International Society for Cell & Gene Therapy Position Paper: Key considerations to support evidence-based cell and gene therapies and oppose marketing of unproven products

<!DOCTYPE html> <html lang="en" class="pb-page" data-request-id="54c5a293-8d8d-41d1-9888-491c16eb2b67" ><head data-pb-dropzone="head"><meta name="pbContext" content=";issue:issue:pii\:S1465324922X00224;ctype:string:Journal Content;requestedJournal:journal:jcyt;article:article:pii\:S1465324923000646;website:website:jcyt-site;pageGroup:string:Article View;journal:journal:jcyt;wgroup:string:Migrated Websites;page:string:Show Full Text;subPage:string:Full Text;product:product:elsevier\:product\:ha"/>  <meta name="robots" content="noarchive,nocache" /> <meta name="viewport" content=""width=device-width,initial-scale=1,maximum-scale=1, user-scalable=1"/> <meta property="og:title" content="International Society for Cell & Gene Therapy Position Paper: Key considerations to support evidence-based cell and gene therapies and oppose marketing of unproven products" /> <meta property="og:type" content="Article" /> <meta property="og:url" content="https://www.isct-cytotherapy.org/article/S1465-3249(23)00064-6/abstract" /> <meta property="og:site_name" content="Cytotherapy" /> <meta property="og:description" content="The field of regenerative medicine, including cellular immunotherapies, is on a remarkable growth trajectory. Dozens of cell-, tissue- and gene-based products have received marketing authorization worldwide while hundreds-to-thousands are either in preclinical development or under clinical investigation in phased clinical trials. However, the promise of regenerative therapies has also given rise to a global industry of direct-to-consumer offerings of prematurely commercialized cell and cell-based products with unknown safety and efficacy profiles." /> <meta name="twitter:title" content="International Society for Cell & Gene Therapy Position Paper: Key considerations to support evidence-based cell and gene therapies and oppose marketing of unproven products" /> <meta name="twitter:description" content="The field of regenerative medicine, including cellular immunotherapies, is on a remarkable growth trajectory. Dozens of cell-, tissue- and gene-based products have received marketing authorization worldwide while hundreds-to-thousands are either in preclinical development or under clinical investigation in phased clinical trials. However, the promise of regenerative therapies has also given rise to a global industry of direct-to-consumer offerings of prematurely commercialized cell and cell-based products with unknown safety and efficacy profiles." /> <meta name="twitter:card" content="summary_large_image"> <link rel="canonical" href="https://www.isct-cytotherapy.org/article/S1465-3249(23)00064-6/fulltext"> <title>International Society for Cell & Gene Therapy Position Paper: Key considerations to support evidence-based cell and gene therapies and oppose marketing of unproven products - Cytotherapy</title><meta name="citation_journal_title" content="Cytotherapy"/> <meta name="citation_journal_abbrev" content="Cytotherapy"/> <meta name="citation_publisher" content="Elsevier"/> <meta name="citation_title" content="International Society for Cell & Gene Therapy Position Paper: Key considerations to support evidence-based cell and gene therapies and oppose marketing of unproven products"/> <meta name="citation_date" content="2023/09/01"/> <meta name="citation_volume" content="25"/> <meta name="citation_issue" content="9"/> <meta name="citation_firstpage" content="920"/> <meta name="citation_lastpage" content="929"/> <meta name="citation_pmid" content="37517865"/> <meta name="citation_abstract_html_url" content="http://www.isct-cytotherapy.org/article/S1465324923000646/abstract"/> <meta name="citation_fulltext_html_url" content="http://www.isct-cytotherapy.org/article/S1465324923000646/fulltext"/> <meta name="citation_pdf_url" content="http://www.isct-cytotherapy.org/article/S1465324923000646/pdf"/> <meta name="citation_issn" content="1465-3249"/> <meta name="citation_language" content="English"/> <meta name="citation_doi" content="10.1016/j.jcyt.2023.03.002"/> <meta name="citation_pmid" content="37517865"/> <meta name="citation_author" content="Laertis Ikonomou"></meta><meta name="citation_author_email" content="laertisi@buffalo.edu"></meta><meta name="citation_author_orcid" content="0000-0003-0993-6713"></meta><meta name="citation_author_institution" content="Department of Oral Biology, University at Buffalo, The State University of New York, Buffalo, New York, USA"></meta><meta name="citation_author_institution" content="Cell, Gene and Tissue Engineering Center, University at Buffalo, The State University of New York, Buffalo, New York, USA"></meta><meta name="citation_author" content="Natividad Cuende"></meta><meta name="citation_author_institution" content="Andalusian Transplant Coordination, Servicio Andaluz de Salud; Sevilla, Spain"></meta><meta name="citation_author" content="Miguel Forte"></meta><meta name="citation_author_orcid" content="0000-0002-0584-0389"></meta><meta name="citation_author_institution" content="AdBio Partners, Paris, France"></meta><meta name="citation_author" content="Bambi J. Grilley"></meta><meta name="citation_author_institution" content="Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, Houston Methodist Hospital, Houston, Texas, USA"></meta><meta name="citation_author_institution" content="Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA"></meta><meta name="citation_author" content="Aaron D. Levine"></meta><meta name="citation_author_institution" content="School of Public Policy, Georgia Institute of Technology, Atlanta, Georgia, USA"></meta><meta name="citation_author" content="Megan Munsie"></meta><meta name="citation_author_institution" content="Melbourne Medical School, University of Melbourne, Parkville, Victoria, Australia"></meta><meta name="citation_author_institution" content="Murdoch Children's Research Institute, Parkville, Victoria, Australia"></meta><meta name="citation_author" content="John E.J. Rasko"></meta><meta name="citation_author_orcid" content="0000-0003-2975-807X"></meta><meta name="citation_author_institution" content="Gene and Stem Cell Therapy Program Centenary Institute, University of Sydney, Sydney, NSW, Australia"></meta><meta name="citation_author_institution" content="Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia"></meta><meta name="citation_author_institution" content="Cell & Molecular Therapies, Royal Prince Alfred Hospital, Camperdown, NSW, Australia"></meta><meta name="citation_author" content="Leigh Turner"></meta><meta name="citation_author_orcid" content="0000-0001-7283-6809"></meta><meta name="citation_author_institution" content="Department of Health, Society, and Behavior, Program in Public Health; Stem Cell Research Center; Institute for Clinical and Translational Science; Department of Family Medicine; University of California, Irvine; Irvine, California, USA"></meta><meta name="citation_author" content="Hamid R. Bidkhori"></meta><meta name="citation_author_orcid" content="0000-0002-0204-0351"></meta><meta name="citation_author_institution" content="Stem Cell and Regenerative Medicine Research Department, Academic Center for Education, Culture and Research (ACECR)-Khorasan Razavi, Mashhad, Iran"></meta><meta name="citation_author" content="Rachele Ciccocioppo"></meta><meta name="citation_author_orcid" content="0000-0002-6297-7576"></meta><meta name="citation_author_institution" content="Gastroenterology Unit, Department of Medicine, A.O.U.I. Policlinico G.B. Rossi & University of Verona, Verona, Italy"></meta><meta name="citation_author" content="Felix Grignon"></meta><meta name="citation_author_institution" content="International Society for Cell & Gene Therapy, Vancouver, Canada"></meta><meta name="citation_author" content="Alok Srivastava"></meta><meta name="citation_author_institution" content="Department of Haematology, Christian Medical College, Ranipet Campus, Ranipet & Centre for Stem Cell Research (a unit of inStem Bengaluru) CMC Campus, Vellore, India"></meta><meta name="citation_author" content="Daniel J. Weiss"></meta><meta name="citation_author_institution" content="University of Vermont College of Medicine, Burlington, Vermont, USA"></meta><meta name="citation_author" content="Patricia Zettler"></meta><meta name="citation_author_orcid" content="0000-0001-9114-0735"></meta><meta name="citation_author_institution" content="Moritz College of Law, Drug Enforcement and Policy Center, Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA"></meta><meta name="citation_author" content="Bruce L. Levine"></meta><meta name="citation_author_institution" content="Center for Cellular Immunotherapies, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, Pennsylvania, USA"></meta><meta name="citation_keywords" content="cell and gene therapies (CGTs); regulatory agencies; reporting mechanisms; tokens of scientific legitimacy; unproven cell and gene interventions"></meta><meta name="citation_reference" content="ISCT Presidential Task Force on the Use of Unproven Cellular Therapies, Reference Guide, 2015. https://www.isctglobal.org/about/isct-committees/ecgt/ptfreferenceguide. (Accessed March 3 2023)."></meta><meta name="citation_reference" content="citation_title=Weighing up the evidence used by direct-to-consumer stem cell businesses; citation_author=M. Cook; citation_author=A. Richey; citation_author=D.A. Brafman; citation_author=E.K. Frow; citation_journal_title=Stem Cell Rep; citation_volume=16; citation_number=12; citation_firstpage=2852; citation_lastpage=2860; citation_publication_date=2021; "></meta><meta name="citation_reference" content="citation_title=ClinicalTrials.gov, stem cells and 'pay-to-participate' clinical studies; citation_author=L. Turner; citation_journal_title=Regen. Med.; citation_volume=12; citation_number=6; citation_firstpage=705; citation_lastpage=719; citation_publication_date=2017; "></meta><meta name="citation_reference" content="citation_title=Co-opting of ClinicalTrials.gov by patient-funded studies; citation_author=D.E. Wagner; citation_author=L. Turner; citation_author=A. Panoskaltsis-Mortari; citation_author=D.J. Weiss; citation_author=L. Ikonomou; citation_journal_title=Lancet Resp. Med.; citation_volume=6; citation_number=8; citation_firstpage=579; citation_lastpage=581; citation_publication_date=2018; "></meta><meta name="citation_reference" content="citation_title=Science, misinformation, and the role of education; citation_author=J. Osborne; citation_author=D. Pimentel; citation_journal_title=Science; citation_volume=378; citation_number=6617; citation_firstpage=246; citation_lastpage=248; citation_publication_date=2022; "></meta><meta name="citation_reference" content="citation_title=Cell banking for cell and gene therapy-regulatory, ethical, and scientific considerations; citation_author=L. Ikonomou; citation_author=A.D. Levine; citation_author=P. Hematti; citation_author=B.L. Levine; citation_journal_title=Bioprocess Int; citation_volume=18; citation_number=1-2)i; citation_publication_date=2020; "></meta><meta name="citation_reference" content="citation_title=Part 1: defining unproven cellular therapies; citation_author=A. Srivastava; citation_author=C. Mason; citation_author=E. Wagena; citation_author=N. Cuende; citation_author=D.J. Weiss; citation_author=E.M. Horwitz; citation_author=M. Dominici; citation_journal_title=Cytotherapy; citation_volume=18; citation_number=1; citation_firstpage=117; citation_lastpage=119; citation_publication_date=2016; "></meta><meta name="citation_reference" content="citation_title=Open for business: a comparative study of websites selling autologous stem cells in Australia and Japan; citation_author=M. Munsie; citation_author=T. Lysaght; citation_author=T. Hendl; citation_author=H.Y.L. Tan; citation_author=I. Kerridge; citation_author=C. Stewart; citation_journal_title=Regen. Med.; citation_volume=12; citation_number=7; citation_firstpage=777; citation_lastpage=790; citation_publication_date=2017; "></meta><meta name="citation_reference" content="citation_title=Selling stem cell 'treatments' as research: prospective customer perspectives from crowdfunding campaigns; citation_author=J. Snyder; citation_author=L. Turner; citation_journal_title=Regen. Med.; citation_volume=13; citation_number=4; citation_firstpage=375; citation_lastpage=384; citation_publication_date=2018; "></meta><meta name="citation_reference" content="citation_title=Marketing of unproven stem cell-based interventions: a call to action; citation_author=D. Sipp; citation_author=T. Caulfield; citation_author=J. Kaye; citation_author=J. Barfoot; citation_author=C. Blackburn; citation_author=S. Chan; citation_author=et al.; citation_journal_title=Sci Transl Med; citation_volume=9; citation_number=397; citation_publication_date=2017; "></meta><meta name="citation_reference" content="citation_title=FDA regulation of stem cell-based products; citation_author=D.W. Fink; citation_journal_title=Science; citation_volume=324; citation_number=5935; citation_firstpage=1662; citation_lastpage=1663; citation_publication_date=2009; "></meta><meta name="citation_reference" content="citation_title=From bench to FDA to bedside: US regulatory trends for new stem cell therapies; citation_author=P.S. Knoepfler; citation_journal_title=Adv Drug Deliv Rev; citation_volume=82-83; citation_firstpage=192; citation_lastpage=196; citation_publication_date=2015; "></meta><meta name="citation_reference" content="citation_title=Food & Drug Administration; citation_publication_date=2021; citation_publisher=Regenerative Medicine Advanced Therapy Designation; "></meta><meta name="citation_reference" content="citation_title=PRIME: priority medicines; citation_author=European Medicines Agency; citation_publication_date=2021; "></meta><meta name="citation_reference" content="citation_title=Strategy of SAKIGAKE; citation_author=Ministry of Health, Labour and Welfare (MHLW); citation_publication_date=2021; "></meta><meta name="citation_reference" content="citation_title=Approved cellular and gene therapy products; citation_author=Food & Drug Administration; citation_publication_date=2022; "></meta><meta name="citation_reference" content="citation_title=Cell, tissue and gene products with marketing authorization in 2018 worldwide; citation_author=N. Cuende; citation_author=J.E.J. Rasko; citation_author=M.B.C. Koh; citation_author=M. Dominici; citation_author=L. Ikonomou; citation_journal_title=Cytotherapy; citation_volume=20; citation_number=11; citation_firstpage=1401; citation_lastpage=1413; citation_publication_date=2018; "></meta><meta name="citation_reference" content="citation_title=The puzzling situation of hospital exemption for advanced therapy medicinal products in Europe and stakeholders' concerns; citation_author=N. Cuende; citation_author=C. Boniface; citation_author=C. Bravery; citation_author=M. Forte; citation_author=R. Giordano; citation_author=M. Hildebrandt; citation_author=A. Izeta; citation_author=M. Dominici; citation_journal_title=Cytotherapy; citation_volume=16; citation_number=12; citation_firstpage=1597; citation_lastpage=1600; citation_publication_date=2014; "></meta><meta name="citation_reference" content="citation_title=Patient access to and ethical considerations of the application of the European Union hospital exemption rule for advanced therapy medicinal products; citation_author=N. Cuende; citation_author=R. Ciccocioppo; citation_author=M. Forte; citation_author=J. Galipeau; citation_author=L. Ikonomou; citation_author=B.L. Levine; citation_author=A. Srivastava; citation_author=P.J. Zettler; citation_journal_title=Cytotherapy; citation_volume=24; citation_number=7; citation_firstpage=686; citation_lastpage=690; citation_publication_date=2022; "></meta><meta name="citation_reference" content="citation_title=Balancing safety and innovation for cell-based regenerative medicine; citation_author=P. Marks; citation_author=S. Gottlieb; citation_journal_title=N. Engl. J. Med.; citation_volume=378; citation_number=10; citation_firstpage=954; citation_lastpage=959; citation_publication_date=2018; "></meta><meta name="citation_reference" content="citation_title=Downgrading of regulation in regenerative medicine; citation_author=D. Sipp; citation_author=M. Sleeboom-Faulkner; citation_journal_title=Science; citation_volume=365; citation_number=6454; citation_firstpage=644; citation_lastpage=646; citation_publication_date=2019; "></meta><meta name="citation_reference" content="citation_title=Concise review: a comprehensive analysis of reported adverse events in patients receiving unproven stem cell-based interventions; citation_author=G. Bauer; citation_author=M. Elsallab; citation_author=M. Abou-El-Enein; citation_journal_title=Stem Cells Transl. Med.; citation_volume=7; citation_number=9; citation_firstpage=676; citation_lastpage=685; citation_publication_date=2018; "></meta><meta name="citation_reference" content="citation_title=The deadly business of an unregulated global stem cell industry; citation_author=T. Lysaght; citation_author=W. Lipworth; citation_author=T. Hendl; citation_author=I. Kerridge; citation_author=T.L. Lee; citation_author=M. Munsie; citation_author=C. Waldby; citation_author=C. Stewart; citation_journal_title=J. Med. Ethics; citation_volume=43; citation_number=11; citation_firstpage=744; citation_lastpage=746; citation_publication_date=2017; "></meta><meta name="citation_reference" content="citation_title=Harms Linked to Unapproved Stem Cell Interventions Highlight Need for Greater FDA Enforcement; citation_author=L. Richardson; citation_publication_date=2021; citation_publisher=The Pew Charitable Trusts; "></meta><meta name="citation_reference" content="N. Ortolano, How do you separate scientifically sound stem cell therapies from scams?, 2020. https://www.statnews.com/2020/08/18/separate-scientific-scam-stem-cell/. (Accessed March 3 2023)."></meta><meta name="citation_reference" content="citation_title=Crowdfunding for unproven stem cell-based interventions; citation_author=J. Snyder; citation_author=L. Turner; citation_author=V.A. Crooks; citation_journal_title=JAMA-J. Am. Med. Assoc.; citation_volume=319; citation_number=18; citation_firstpage=1935; citation_lastpage=1936; citation_publication_date=2018; "></meta><meta name="citation_reference" content="citation_title=Committee for Advanced Therapies (CAT), EMA warns against using unproven cell-based therapies; citation_author=European Medicines Agency (EMA); citation_publication_date=2020; "></meta><meta name="citation_reference" content="citation_title=FDA Warns About Stem Cell Therapies; citation_author=Food & Drug Administration; citation_publication_date=2019; "></meta><meta name="citation_reference" content="citation_title=How to peddle hope: an analysis of youtube patient testimonials of unproven stem cell treatments; citation_author=B. Hawke; citation_author=A.R. Przybylo; citation_author=D. Paciulli; citation_author=T. Caulfield; citation_author=A. Zarzeczny; citation_author=Z. Master; citation_journal_title=Stem Cell Rep; citation_volume=12; citation_number=6; citation_firstpage=1186; citation_lastpage=1189; citation_publication_date=2019; "></meta><meta name="citation_reference" content="citation_title=The International Conference on Harmonization Good Clinical Practice guideline; citation_author=J.R. Dixon; citation_journal_title=Qual Assur; citation_volume=6; citation_number=2; citation_firstpage=65; citation_lastpage=74; citation_publication_date=1998; "></meta><meta name="citation_reference" content="citation_title=Food & Drug Administration; citation_publication_date=2020; citation_publisher=Consumer Alert on Regenerative Medicine Products Including Stem Cells and Exosomes; "></meta><meta name="citation_reference" content="citation_title=Ethical issues and public communication in the development of cell-based treatments for COVID-19: lessons from the pandemic; citation_author=L. Turner; citation_author=M. Munsie; citation_author=A.D. Levine; citation_author=L. Ikonomou; citation_journal_title=Stem Cell Rep; citation_volume=16; citation_number=11; citation_firstpage=2567; citation_lastpage=2576; citation_publication_date=2021; "></meta><meta name="citation_reference" content="citation_title=The roles and responsibilities of physicians in patients' decisions about unproven stem cell therapies; citation_author=A.D. Levine; citation_author=L.E. Wolf; citation_journal_title=J. Law Med.Ethics; citation_volume=40; citation_number=1; citation_firstpage=122; citation_lastpage=134; citation_publication_date=2012; "></meta><meta name="citation_reference" content="citation_title=Medical societies, patient education initiatives, public debate and marketing of unproven stem cell interventions; citation_author=D.J. Weiss; citation_author=L. Turner; citation_author=A.D. Levine; citation_author=L. Ikonomou; citation_journal_title=Cytotherapy; citation_volume=20; citation_number=2; citation_firstpage=165; citation_lastpage=168; citation_publication_date=2018; "></meta><meta name="citation_reference" content="citation_title=Health Canada; citation_publication_date=2019; citation_publisher=Health Canada is advising Canadians about the potential health risks associated with unauthorized cell therapy treatments such as stem cell therapy; "></meta><meta name="citation_reference" content="citation_title=Health Canada; citation_publication_date=2020; citation_publisher=Health Canada Policy Position Paper – Autologous Cell Therapy Products; "></meta><meta name="citation_reference" content="J.S. Eglovitch, WHO charts path to convergence on cell and gene therapies, 2022. https://www.raps.org/news-and-articles/news-articles/2022/1/who-charts-path-to-convergence-on-cell-and-gene-th. (Accessed March 3 2023)."></meta><meta name="citation_reference" content="citation_title=Unproven stem cell interventions: a global public health problem requiring global deliberation; citation_author=Z. Master; citation_author=K.R.W. Matthews; citation_author=M. Abou-el-Enein; citation_journal_title=Stem Cell Rep; citation_volume=16; citation_number=6; citation_firstpage=1435; citation_lastpage=1445; citation_publication_date=2021; "></meta><meta name="citation_reference" content="citation_title=Medical crowdfunding for scientifically unsupported or potentially dangerous treatments; citation_author=F. Vox; citation_author=K.M. Folkers; citation_author=A. Turi; citation_author=A.L. Caplan; citation_journal_title=JAMA-J. Am. Med. Assoc.; citation_volume=320; citation_number=16; citation_firstpage=1705; citation_lastpage=1706; citation_publication_date=2018; "></meta><meta name="citation_reference" content="citation_title=The stem cell hard sell: report from a clinic's patient recruitment seminar; citation_author=P.S. Knoepfler; citation_journal_title=Stem Cells Transl. Med.; citation_volume=6; citation_number=1; citation_firstpage=14; citation_lastpage=16; citation_publication_date=2017; "></meta><meta name="citation_reference" content="citation_title=Clinic pitches unproven treatments to desperate patients, with tips on raising the cash; citation_author=W. Wan; citation_author=L. McGinley; citation_publication_date=2019; citation_publisher=Washington Post; "></meta><meta name="citation_reference" content="citation_title=Identifying the risks of unproven regenerative medicine therapies; citation_author=P.W. Marks; citation_author=S. Hahn; citation_journal_title=JAMA-J. Am. Med. Assoc.; citation_volume=324; citation_number=3; citation_firstpage=241; citation_lastpage=242; citation_publication_date=2020; "></meta><meta name="citation_reference" content="citation_title=Characteristics and scope of training of clinicians participating in the US direct-to-consumer marketplace for unproven stem cell interventions; citation_author=W. Fu; citation_author=C. Smith; citation_author=L. Turner; citation_author=J. Fojtik; citation_author=J.E. Pacyna; citation_author=Z. Master; citation_journal_title=JAMA-J. Am. Med. Assoc.; citation_volume=321; citation_number=24; citation_firstpage=2462; citation_lastpage=2463; citation_publication_date=2019; "></meta><meta name="citation_reference" content="citation_title=The involvement of Canadian physicians in promoting and providing unproven and unapproved stem cell interventions; citation_author=U. Ogbogu; citation_author=J. Du; citation_author=Y. Koukio; citation_journal_title=BMC Med Ethics; citation_volume=19; citation_publication_date=2018; "></meta><meta name="citation_reference" content="citation_title=Selling stem cells in the USA: assessing the direct-to-consumer industry; citation_author=L. Turner; citation_author=P. Knoepfler; citation_journal_title=Cell Stem Cell; citation_volume=19; citation_number=2; citation_firstpage=154; citation_lastpage=157; citation_publication_date=2016; "></meta><meta name="citation_reference" content="C. Kelly, ‘FTC weighing trade rule on fake endorsements, including by ‘patient ambassadors’, 2020. https://pink.pharmaintelligence.informa.com/PS147174/FTC-Weighing-Trade-Rule-On-Fake-Endorsements-Including-By-Patient-Ambassadors. (Accessed March 3 2023)."></meta><meta name="citation_reference" content="citation_title=Confronting stem cell hype; citation_author=T. Caulfield; citation_author=D. Sipp; citation_author=C.E. Murry; citation_author=G.Q. Daley; citation_author=J. Kimmelman; citation_journal_title=Science; citation_volume=352; citation_number=6287; citation_firstpage=776; citation_lastpage=777; citation_publication_date=2016; "></meta><meta name="citation_abstract" content="<h2>Abstract</h2><p>The field of regenerative medicine, including cellular immunotherapies, is on a remarkable growth trajectory. Dozens of cell-, tissue- and gene-based products have received marketing authorization worldwide while hundreds-to-thousands are either in preclinical development or under clinical investigation in phased clinical trials. However, the promise of regenerative therapies has also given rise to a global industry of direct-to-consumer offerings of prematurely commercialized cell and cell-based products with unknown safety and efficacy profiles. Since its inception, the International Society for Cell & Gene Therapy Committee on the Ethics of Cell and Gene Therapy has opposed the premature commercialization of unproven cell- and gene-based interventions and supported the development of evidence-based advanced therapy products. In the present Guide, targeted at International Society for Cell & Gene Therapy members, we analyze this industry, focusing in particular on distinctive features of unproven cell and cell-based products and the use of tokens of scientific legitimacy as persuasive marketing devices. We also provide an overview of reporting mechanisms for patients who believe they have been harmed by administration of unapproved and unproven products and suggest practical strategies to address the direct-to-consumer marketing of such products. Development of this Guide epitomizes our continued support for the ethical and rigorous development of cell and cell-based products with patient safety and therapeutic benefit as guiding principles.</p>"></meta><meta charset="UTF-8" /> <script type="text/javascript"> ;window.NREUM||(NREUM={});NREUM.init={privacy:{cookies_enabled:true}}; window.NREUM||(NREUM={}),__nr_require=function(t,e,n){function r(n){if(!e[n]){var o=e[n]={exports:{}};t[n][0].call(o.exports,function(e){var o=t[n][1][e];return r(o||e)},o,o.exports)}return e[n].exports}if("function"==typeof __nr_require)return __nr_require;for(var o=0;o<n.length;o++)r(n[o]);return r}({1:[function(t,e,n){function r(t){try{c.console&&console.log(t)}catch(e){}}var o,i=t("ee"),a=t(26),c={};try{o=localStorage.getItem("__nr_flags").split(","),console&&"function"==typeof console.log&&(c.console=!0,o.indexOf("dev")!==-1&&(c.dev=!0),o.indexOf("nr_dev")!==-1&&(c.nrDev=!0))}catch(s){}c.nrDev&&i.on("internal-error",function(t){r(t.stack)}),c.dev&&i.on("fn-err",function(t,e,n){r(n.stack)}),c.dev&&(r("NR AGENT IN DEVELOPMENT MODE"),r("flags: "+a(c,function(t,e){return t}).join(", ")))},{}],2:[function(t,e,n){function r(t,e,n,r,c){try{l?l-=1:o(c||new UncaughtException(t,e,n),!0)}catch(f){try{i("ierr",[f,s.now(),!0])}catch(d){}}return"function"==typeof u&&u.apply(this,a(arguments))}function UncaughtException(t,e,n){this.message=t||"Uncaught error with no additional information",this.sourceURL=e,this.line=n}function o(t,e){var n=e?null:s.now();i("err",[t,n])}var i=t("handle"),a=t(27),c=t("ee"),s=t("loader"),f=t("gos"),u=window.onerror,d=!1,p="nr@seenError",l=0;s.features.err=!0,t(1),window.onerror=r;try{throw new Error}catch(h){"stack"in h&&(t(13),t(12),"addEventListener"in window&&t(6),s.xhrWrappable&&t(14),d=!0)}c.on("fn-start",function(t,e,n){d&&(l+=1)}),c.on("fn-err",function(t,e,n){d&&!n[p]&&(f(n,p,function(){return!0}),this.thrown=!0,o(n))}),c.on("fn-end",function(){d&&!this.thrown&&l>0&&(l-=1)}),c.on("internal-error",function(t){i("ierr",[t,s.now(),!0])})},{}],3:[function(t,e,n){t("loader").features.ins=!0},{}],4:[function(t,e,n){function r(){_++,T=g.hash,this[u]=y.now()}function o(){_--,g.hash!==T&&i(0,!0);var t=y.now();this[h]=~~this[h]+t-this[u],this[d]=t}function i(t,e){E.emit("newURL",[""+g,e])}function a(t,e){t.on(e,function(){this[e]=y.now()})}var c="-start",s="-end",f="-body",u="fn"+c,d="fn"+s,p="cb"+c,l="cb"+s,h="jsTime",m="fetch",v="addEventListener",w=window,g=w.location,y=t("loader");if(w[v]&&y.xhrWrappable){var x=t(10),b=t(11),E=t(8),R=t(6),O=t(13),N=t(7),M=t(14),P=t(9),S=t("ee"),C=S.get("tracer");t(16),y.features.spa=!0;var T,_=0;S.on(u,r),S.on(p,r),S.on(d,o),S.on(l,o),S.buffer([u,d,"xhr-done","xhr-resolved"]),R.buffer([u]),O.buffer(["setTimeout"+s,"clearTimeout"+c,u]),M.buffer([u,"new-xhr","send-xhr"+c]),N.buffer([m+c,m+"-done",m+f+c,m+f+s]),E.buffer(["newURL"]),x.buffer([u]),b.buffer(["propagate",p,l,"executor-err","resolve"+c]),C.buffer([u,"no-"+u]),P.buffer(["new-jsonp","cb-start","jsonp-error","jsonp-end"]),a(M,"send-xhr"+c),a(S,"xhr-resolved"),a(S,"xhr-done"),a(N,m+c),a(N,m+"-done"),a(P,"new-jsonp"),a(P,"jsonp-end"),a(P,"cb-start"),E.on("pushState-end",i),E.on("replaceState-end",i),w[v]("hashchange",i,!0),w[v]("load",i,!0),w[v]("popstate",function(){i(0,_>1)},!0)}},{}],5:[function(t,e,n){function r(t){}if(window.performance&&window.performance.timing&&window.performance.getEntriesByType){var o=t("ee"),i=t("handle"),a=t(13),c=t(12),s="learResourceTimings",f="addEventListener",u="resourcetimingbufferfull",d="bstResource",p="resource",l="-start",h="-end",m="fn"+l,v="fn"+h,w="bstTimer",g="pushState",y=t("loader");y.features.stn=!0,t(8),"addEventListener"in window&&t(6);var x=NREUM.o.EV;o.on(m,function(t,e){var n=t[0];n instanceof x&&(this.bstStart=y.now())}),o.on(v,function(t,e){var n=t[0];n instanceof x&&i("bst",[n,e,this.bstStart,y.now()])}),a.on(m,function(t,e,n){this.bstStart=y.now(),this.bstType=n}),a.on(v,function(t,e){i(w,[e,this.bstStart,y.now(),this.bstType])}),c.on(m,function(){this.bstStart=y.now()}),c.on(v,function(t,e){i(w,[e,this.bstStart,y.now(),"requestAnimationFrame"])}),o.on(g+l,function(t){this.time=y.now(),this.startPath=location.pathname+location.hash}),o.on(g+h,function(t){i("bstHist",[location.pathname+location.hash,this.startPath,this.time])}),f in window.performance&&(window.performance["c"+s]?window.performance[f](u,function(t){i(d,[window.performance.getEntriesByType(p)]),window.performance["c"+s]()},!1):window.performance[f]("webkit"+u,function(t){i(d,[window.performance.getEntriesByType(p)]),window.performance["webkitC"+s]()},!1)),document[f]("scroll",r,{passive:!0}),document[f]("keypress",r,!1),document[f]("click",r,!1)}},{}],6:[function(t,e,n){function r(t){for(var e=t;e&&!e.hasOwnProperty(u);)e=Object.getPrototypeOf(e);e&&o(e)}function o(t){c.inPlace(t,[u,d],"-",i)}function i(t,e){return t[1]}var a=t("ee").get("events"),c=t("wrap-function")(a,!0),s=t("gos"),f=XMLHttpRequest,u="addEventListener",d="removeEventListener";e.exports=a,"getPrototypeOf"in Object?(r(document),r(window),r(f.prototype)):f.prototype.hasOwnProperty(u)&&(o(window),o(f.prototype)),a.on(u+"-start",function(t,e){var n=t[1],r=s(n,"nr@wrapped",function(){function t(){if("function"==typeof n.handleEvent)return n.handleEvent.apply(n,arguments)}var e={object:t,"function":n}[typeof n];return e?c(e,"fn-",null,e.name||"anonymous"):n});this.wrapped=t[1]=r}),a.on(d+"-start",function(t){t[1]=this.wrapped||t[1]})},{}],7:[function(t,e,n){function r(t,e,n){var r=t[e];"function"==typeof r&&(t[e]=function(){var t=i(arguments),e={};o.emit(n+"before-start",[t],e);var a;e[m]&&e[m].dt&&(a=e[m].dt);var c=r.apply(this,t);return o.emit(n+"start",[t,a],c),c.then(function(t){return o.emit(n+"end",[null,t],c),t},function(t){throw o.emit(n+"end",[t],c),t})})}var o=t("ee").get("fetch"),i=t(27),a=t(26);e.exports=o;var c=window,s="fetch-",f=s+"body-",u=["arrayBuffer","blob","json","text","formData"],d=c.Request,p=c.Response,l=c.fetch,h="prototype",m="nr@context";d&&p&&l&&(a(u,function(t,e){r(d[h],e,f),r(p[h],e,f)}),r(c,"fetch",s),o.on(s+"end",function(t,e){var n=this;if(e){var r=e.headers.get("content-length");null!==r&&(n.rxSize=r),o.emit(s+"done",[null,e],n)}else o.emit(s+"done",[t],n)}))},{}],8:[function(t,e,n){var r=t("ee").get("history"),o=t("wrap-function")(r);e.exports=r;var i=window.history&&window.history.constructor&&window.history.constructor.prototype,a=window.history;i&&i.pushState&&i.replaceState&&(a=i),o.inPlace(a,["pushState","replaceState"],"-")},{}],9:[function(t,e,n){function r(t){function e(){s.emit("jsonp-end",[],p),t.removeEventListener("load",e,!1),t.removeEventListener("error",n,!1)}function n(){s.emit("jsonp-error",[],p),s.emit("jsonp-end",[],p),t.removeEventListener("load",e,!1),t.removeEventListener("error",n,!1)}var r=t&&"string"==typeof t.nodeName&&"script"===t.nodeName.toLowerCase();if(r){var o="function"==typeof t.addEventListener;if(o){var a=i(t.src);if(a){var u=c(a),d="function"==typeof u.parent[u.key];if(d){var p={};f.inPlace(u.parent,[u.key],"cb-",p),t.addEventListener("load",e,!1),t.addEventListener("error",n,!1),s.emit("new-jsonp",[t.src],p)}}}}}function o(){return"addEventListener"in window}function i(t){var e=t.match(u);return e?e[1]:null}function a(t,e){var n=t.match(p),r=n[1],o=n[3];return o?a(o,e[r]):e[r]}function c(t){var e=t.match(d);return e&&e.length>=3?{key:e[2],parent:a(e[1],window)}:{key:t,parent:window}}var s=t("ee").get("jsonp"),f=t("wrap-function")(s);if(e.exports=s,o()){var u=/[?&](?:callback|cb)=([^&#]+)/,d=/(.*)\.([^.]+)/,p=/^(\w+)(\.|$)(.*)$/,l=["appendChild","insertBefore","replaceChild"];Node&&Node.prototype&&Node.prototype.appendChild?f.inPlace(Node.prototype,l,"dom-"):(f.inPlace(HTMLElement.prototype,l,"dom-"),f.inPlace(HTMLHeadElement.prototype,l,"dom-"),f.inPlace(HTMLBodyElement.prototype,l,"dom-")),s.on("dom-start",function(t){r(t[0])})}},{}],10:[function(t,e,n){var r=t("ee").get("mutation"),o=t("wrap-function")(r),i=NREUM.o.MO;e.exports=r,i&&(window.MutationObserver=function(t){return this instanceof i?new i(o(t,"fn-")):i.apply(this,arguments)},MutationObserver.prototype=i.prototype)},{}],11:[function(t,e,n){function r(t){var e=a.context(),n=c(t,"executor-",e),r=new f(n);return a.context(r).getCtx=function(){return e},a.emit("new-promise",[r,e],e),r}function o(t,e){return e}var i=t("wrap-function"),a=t("ee").get("promise"),c=i(a),s=t(26),f=NREUM.o.PR;e.exports=a,f&&(window.Promise=r,["all","race"].forEach(function(t){var e=f[t];f[t]=function(n){function r(t){return function(){a.emit("propagate",[null,!o],i),o=o||!t}}var o=!1;s(n,function(e,n){Promise.resolve(n).then(r("all"===t),r(!1))});var i=e.apply(f,arguments),c=f.resolve(i);return c}}),["resolve","reject"].forEach(function(t){var e=f[t];f[t]=function(t){var n=e.apply(f,arguments);return t!==n&&a.emit("propagate",[t,!0],n),n}}),f.prototype["catch"]=function(t){return this.then(null,t)},f.prototype=Object.create(f.prototype,{constructor:{value:r}}),s(Object.getOwnPropertyNames(f),function(t,e){try{r[e]=f[e]}catch(n){}}),a.on("executor-start",function(t){t[0]=c(t[0],"resolve-",this),t[1]=c(t[1],"resolve-",this)}),a.on("executor-err",function(t,e,n){t[1](n)}),c.inPlace(f.prototype,["then"],"then-",o),a.on("then-start",function(t,e){this.promise=e,t[0]=c(t[0],"cb-",this),t[1]=c(t[1],"cb-",this)}),a.on("then-end",function(t,e,n){this.nextPromise=n;var r=this.promise;a.emit("propagate",[r,!0],n)}),a.on("cb-end",function(t,e,n){a.emit("propagate",[n,!0],this.nextPromise)}),a.on("propagate",function(t,e,n){this.getCtx&&!e||(this.getCtx=function(){if(t instanceof Promise)var e=a.context(t);return e&&e.getCtx?e.getCtx():this})}),r.toString=function(){return""+f})},{}],12:[function(t,e,n){var r=t("ee").get("raf"),o=t("wrap-function")(r),i="equestAnimationFrame";e.exports=r,o.inPlace(window,["r"+i,"mozR"+i,"webkitR"+i,"msR"+i],"raf-"),r.on("raf-start",function(t){t[0]=o(t[0],"fn-")})},{}],13:[function(t,e,n){function r(t,e,n){t[0]=a(t[0],"fn-",null,n)}function o(t,e,n){this.method=n,this.timerDuration=isNaN(t[1])?0:+t[1],t[0]=a(t[0],"fn-",this,n)}var i=t("ee").get("timer"),a=t("wrap-function")(i),c="setTimeout",s="setInterval",f="clearTimeout",u="-start",d="-";e.exports=i,a.inPlace(window,[c,"setImmediate"],c+d),a.inPlace(window,[s],s+d),a.inPlace(window,[f,"clearImmediate"],f+d),i.on(s+u,r),i.on(c+u,o)},{}],14:[function(t,e,n){function r(t,e){d.inPlace(e,["onreadystatechange"],"fn-",c)}function o(){var t=this,e=u.context(t);t.readyState>3&&!e.resolved&&(e.resolved=!0,u.emit("xhr-resolved",[],t)),d.inPlace(t,g,"fn-",c)}function i(t){y.push(t),h&&(b?b.then(a):v?v(a):(E=-E,R.data=E))}function a(){for(var t=0;t<y.length;t++)r([],y[t]);y.length&&(y=[])}function c(t,e){return e}function s(t,e){for(var n in t)e[n]=t[n];return e}t(6);var f=t("ee"),u=f.get("xhr"),d=t("wrap-function")(u),p=NREUM.o,l=p.XHR,h=p.MO,m=p.PR,v=p.SI,w="readystatechange",g=["onload","onerror","onabort","onloadstart","onloadend","onprogress","ontimeout"],y=[];e.exports=u;var x=window.XMLHttpRequest=function(t){var e=new l(t);try{u.emit("new-xhr",[e],e),e.addEventListener(w,o,!1)}catch(n){try{u.emit("internal-error",[n])}catch(r){}}return e};if(s(l,x),x.prototype=l.prototype,d.inPlace(x.prototype,["open","send"],"-xhr-",c),u.on("send-xhr-start",function(t,e){r(t,e),i(e)}),u.on("open-xhr-start",r),h){var b=m&&m.resolve();if(!v&&!m){var E=1,R=document.createTextNode(E);new h(a).observe(R,{characterData:!0})}}else f.on("fn-end",function(t){t[0]&&t[0].type===w||a()})},{}],15:[function(t,e,n){function r(t){if(!c(t))return null;var e=window.NREUM;if(!e.loader_config)return null;var n=(e.loader_config.accountID||"").toString()||null,r=(e.loader_config.agentID||"").toString()||null,f=(e.loader_config.trustKey||"").toString()||null;if(!n||!r)return null;var h=l.generateSpanId(),m=l.generateTraceId(),v=Date.now(),w={spanId:h,traceId:m,timestamp:v};return(t.sameOrigin||s(t)&&p())&&(w.traceContextParentHeader=o(h,m),w.traceContextStateHeader=i(h,v,n,r,f)),(t.sameOrigin&&!u()||!t.sameOrigin&&s(t)&&d())&&(w.newrelicHeader=a(h,m,v,n,r,f)),w}function o(t,e){return"00-"+e+"-"+t+"-01"}function i(t,e,n,r,o){var i=0,a="",c=1,s="",f="";return o+"@nr="+i+"-"+c+"-"+n+"-"+r+"-"+t+"-"+a+"-"+s+"-"+f+"-"+e}function a(t,e,n,r,o,i){var a="btoa"in window&&"function"==typeof window.btoa;if(!a)return null;var c={v:[0,1],d:{ty:"Browser",ac:r,ap:o,id:t,tr:e,ti:n}};return i&&r!==i&&(c.d.tk=i),btoa(JSON.stringify(c))}function c(t){return f()&&s(t)}function s(t){var e=!1,n={};if("init"in NREUM&&"distributed_tracing"in NREUM.init&&(n=NREUM.init.distributed_tracing),t.sameOrigin)e=!0;else if(n.allowed_origins instanceof Array)for(var r=0;r<n.allowed_origins.length;r++){var o=h(n.allowed_origins[r]);if(t.hostname===o.hostname&&t.protocol===o.protocol&&t.port===o.port){e=!0;break}}return e}function f(){return"init"in NREUM&&"distributed_tracing"in NREUM.init&&!!NREUM.init.distributed_tracing.enabled}function u(){return"init"in NREUM&&"distributed_tracing"in NREUM.init&&!!NREUM.init.distributed_tracing.exclude_newrelic_header}function d(){return"init"in NREUM&&"distributed_tracing"in NREUM.init&&NREUM.init.distributed_tracing.cors_use_newrelic_header!==!1}function p(){return"init"in NREUM&&"distributed_tracing"in NREUM.init&&!!NREUM.init.distributed_tracing.cors_use_tracecontext_headers}var l=t(23),h=t(17);e.exports={generateTracePayload:r,shouldGenerateTrace:c}},{}],16:[function(t,e,n){function r(t){var e=this.params,n=this.metrics;if(!this.ended){this.ended=!0;for(var r=0;r<p;r++)t.removeEventListener(d[r],this.listener,!1);e.aborted||(n.duration=a.now()-this.startTime,this.loadCaptureCalled||4!==t.readyState?null==e.status&&(e.status=0):i(this,t),n.cbTime=this.cbTime,u.emit("xhr-done",[t],t),c("xhr",[e,n,this.startTime]))}}function o(t,e){var n=s(e),r=t.params;r.host=n.hostname+":"+n.port,r.pathname=n.pathname,t.parsedOrigin=s(e),t.sameOrigin=t.parsedOrigin.sameOrigin}function i(t,e){t.params.status=e.status;var n=v(e,t.lastSize);if(n&&(t.metrics.rxSize=n),t.sameOrigin){var r=e.getResponseHeader("X-NewRelic-App-Data");r&&(t.params.cat=r.split(", ").pop())}t.loadCaptureCalled=!0}var a=t("loader");if(a.xhrWrappable){var c=t("handle"),s=t(17),f=t(15).generateTracePayload,u=t("ee"),d=["load","error","abort","timeout"],p=d.length,l=t("id"),h=t(21),m=t(20),v=t(18),w=window.XMLHttpRequest;a.features.xhr=!0,t(14),t(7),u.on("new-xhr",function(t){var e=this;e.totalCbs=0,e.called=0,e.cbTime=0,e.end=r,e.ended=!1,e.xhrGuids={},e.lastSize=null,e.loadCaptureCalled=!1,t.addEventListener("load",function(n){i(e,t)},!1),h&&(h>34||h<10)||window.opera||t.addEventListener("progress",function(t){e.lastSize=t.loaded},!1)}),u.on("open-xhr-start",function(t){this.params={method:t[0]},o(this,t[1]),this.metrics={}}),u.on("open-xhr-end",function(t,e){"loader_config"in NREUM&&"xpid"in NREUM.loader_config&&this.sameOrigin&&e.setRequestHeader("X-NewRelic-ID",NREUM.loader_config.xpid);var n=f(this.parsedOrigin);if(n){var r=!1;n.newrelicHeader&&(e.setRequestHeader("newrelic",n.newrelicHeader),r=!0),n.traceContextParentHeader&&(e.setRequestHeader("traceparent",n.traceContextParentHeader),n.traceContextStateHeader&&e.setRequestHeader("tracestate",n.traceContextStateHeader),r=!0),r&&(this.dt=n)}}),u.on("send-xhr-start",function(t,e){var n=this.metrics,r=t[0],o=this;if(n&&r){var i=m(r);i&&(n.txSize=i)}this.startTime=a.now(),this.listener=function(t){try{"abort"!==t.type||o.loadCaptureCalled||(o.params.aborted=!0),("load"!==t.type||o.called===o.totalCbs&&(o.onloadCalled||"function"!=typeof e.onload))&&o.end(e)}catch(n){try{u.emit("internal-error",[n])}catch(r){}}};for(var c=0;c<p;c++)e.addEventListener(d[c],this.listener,!1)}),u.on("xhr-cb-time",function(t,e,n){this.cbTime+=t,e?this.onloadCalled=!0:this.called+=1,this.called!==this.totalCbs||!this.onloadCalled&&"function"==typeof n.onload||this.end(n)}),u.on("xhr-load-added",function(t,e){var n=""+l(t)+!!e;this.xhrGuids&&!this.xhrGuids[n]&&(this.xhrGuids[n]=!0,this.totalCbs+=1)}),u.on("xhr-load-removed",function(t,e){var n=""+l(t)+!!e;this.xhrGuids&&this.xhrGuids[n]&&(delete this.xhrGuids[n],this.totalCbs-=1)}),u.on("addEventListener-end",function(t,e){e instanceof w&&"load"===t[0]&&u.emit("xhr-load-added",[t[1],t[2]],e)}),u.on("removeEventListener-end",function(t,e){e instanceof w&&"load"===t[0]&&u.emit("xhr-load-removed",[t[1],t[2]],e)}),u.on("fn-start",function(t,e,n){e instanceof w&&("onload"===n&&(this.onload=!0),("load"===(t[0]&&t[0].type)||this.onload)&&(this.xhrCbStart=a.now()))}),u.on("fn-end",function(t,e){this.xhrCbStart&&u.emit("xhr-cb-time",[a.now()-this.xhrCbStart,this.onload,e],e)}),u.on("fetch-before-start",function(t){function e(t,e){var n=!1;return e.newrelicHeader&&(t.set("newrelic",e.newrelicHeader),n=!0),e.traceContextParentHeader&&(t.set("traceparent",e.traceContextParentHeader),e.traceContextStateHeader&&t.set("tracestate",e.traceContextStateHeader),n=!0),n}var n,r=t[1]||{};"string"==typeof t[0]?n=t[0]:t[0]&&t[0].url&&(n=t[0].url),n&&(this.parsedOrigin=s(n),this.sameOrigin=this.parsedOrigin.sameOrigin);var o=f(this.parsedOrigin);if(o&&(o.newrelicHeader||o.traceContextParentHeader))if("string"==typeof t[0]){var i={};for(var a in r)i[a]=r[a];i.headers=new Headers(r.headers||{}),e(i.headers,o)&&(this.dt=o),t.length>1?t[1]=i:t.push(i)}else t[0]&&t[0].headers&&e(t[0].headers,o)&&(this.dt=o)})}},{}],17:[function(t,e,n){var r={};e.exports=function(t){if(t in r)return r[t];var e=document.createElement("a"),n=window.location,o={};e.href=t,o.port=e.port;var i=e.href.split("://");!o.port&&i[1]&&(o.port=i[1].split("/")[0].split("@").pop().split(":")[1]),o.port&&"0"!==o.port||(o.port="https"===i[0]?"443":"80"),o.hostname=e.hostname||n.hostname,o.pathname=e.pathname,o.protocol=i[0],"/"!==o.pathname.charAt(0)&&(o.pathname="/"+o.pathname);var a=!e.protocol||":"===e.protocol||e.protocol===n.protocol,c=e.hostname===document.domain&&e.port===n.port;return o.sameOrigin=a&&(!e.hostname||c),"/"===o.pathname&&(r[t]=o),o}},{}],18:[function(t,e,n){function r(t,e){var n=t.responseType;return"json"===n&&null!==e?e:"arraybuffer"===n||"blob"===n||"json"===n?o(t.response):"text"===n||""===n||void 0===n?o(t.responseText):void 0}var o=t(20);e.exports=r},{}],19:[function(t,e,n){function r(){}function o(t,e,n){return function(){return i(t,[f.now()].concat(c(arguments)),e?null:this,n),e?void 0:this}}var i=t("handle"),a=t(26),c=t(27),s=t("ee").get("tracer"),f=t("loader"),u=NREUM;"undefined"==typeof window.newrelic&&(newrelic=u);var d=["setPageViewName","setCustomAttribute","setErrorHandler","finished","addToTrace","inlineHit","addRelease"],p="api-",l=p+"ixn-";a(d,function(t,e){u[e]=o(p+e,!0,"api")}),u.addPageAction=o(p+"addPageAction",!0),u.setCurrentRouteName=o(p+"routeName",!0),e.exports=newrelic,u.interaction=function(){return(new r).get()};var h=r.prototype={createTracer:function(t,e){var n={},r=this,o="function"==typeof e;return i(l+"tracer",[f.now(),t,n],r),function(){if(s.emit((o?"":"no-")+"fn-start",[f.now(),r,o],n),o)try{return e.apply(this,arguments)}catch(t){throw s.emit("fn-err",[arguments,this,t],n),t}finally{s.emit("fn-end",[f.now()],n)}}}};a("actionText,setName,setAttribute,save,ignore,onEnd,getContext,end,get".split(","),function(t,e){h[e]=o(l+e)}),newrelic.noticeError=function(t,e){"string"==typeof t&&(t=new Error(t)),i("err",[t,f.now(),!1,e])}},{}],20:[function(t,e,n){e.exports=function(t){if("string"==typeof t&&t.length)return t.length;if("object"==typeof t){if("undefined"!=typeof ArrayBuffer&&t instanceof ArrayBuffer&&t.byteLength)return t.byteLength;if("undefined"!=typeof Blob&&t instanceof Blob&&t.size)return t.size;if(!("undefined"!=typeof FormData&&t instanceof FormData))try{return JSON.stringify(t).length}catch(e){return}}}},{}],21:[function(t,e,n){var r=0,o=navigator.userAgent.match(/Firefox[\/\s](\d+\.\d+)/);o&&(r=+o[1]),e.exports=r},{}],22:[function(t,e,n){function r(t,e){var n=t.getEntries();n.forEach(function(t){"first-paint"===t.name?d("timing",["fp",Math.floor(t.startTime)]):"first-contentful-paint"===t.name&&d("timing",["fcp",Math.floor(t.startTime)])})}function o(t,e){var n=t.getEntries();n.length>0&&d("lcp",[n[n.length-1]])}function i(t){t.getEntries().forEach(function(t){t.hadRecentInput||d("cls",[t])})}function a(t){if(t instanceof h&&!v){var e=Math.round(t.timeStamp),n={type:t.type};e<=p.now()?n.fid=p.now()-e:e>p.offset&&e<=Date.now()?(e-=p.offset,n.fid=p.now()-e):e=p.now(),v=!0,d("timing",["fi",e,n])}}function c(t){d("pageHide",[p.now(),t])}if(!("init"in NREUM&&"page_view_timing"in NREUM.init&&"enabled"in NREUM.init.page_view_timing&&NREUM.init.page_view_timing.enabled===!1)){var s,f,u,d=t("handle"),p=t("loader"),l=t(25),h=NREUM.o.EV;if("PerformanceObserver"in window&&"function"==typeof window.PerformanceObserver){s=new PerformanceObserver(r);try{s.observe({entryTypes:["paint"]})}catch(m){}f=new PerformanceObserver(o);try{f.observe({entryTypes:["largest-contentful-paint"]})}catch(m){}u=new PerformanceObserver(i);try{u.observe({type:"layout-shift",buffered:!0})}catch(m){}}if("addEventListener"in document){var v=!1,w=["click","keydown","mousedown","pointerdown","touchstart"];w.forEach(function(t){document.addEventListener(t,a,!1)})}l(c)}},{}],23:[function(t,e,n){function r(){function t(){return e?15&e[n++]:16*Math.random()|0}var e=null,n=0,r=window.crypto||window.msCrypto;r&&r.getRandomValues&&(e=r.getRandomValues(new Uint8Array(31)));for(var o,i="xxxxxxxx-xxxx-4xxx-yxxx-xxxxxxxxxxxx",a="",c=0;c<i.length;c++)o=i[c],"x"===o?a+=t().toString(16):"y"===o?(o=3&t()|8,a+=o.toString(16)):a+=o;return a}function o(){return a(16)}function i(){return a(32)}function a(t){function e(){return n?15&n[r++]:16*Math.random()|0}var n=null,r=0,o=window.crypto||window.msCrypto;o&&o.getRandomValues&&Uint8Array&&(n=o.getRandomValues(new Uint8Array(31)));for(var i=[],a=0;a<t;a++)i.push(e().toString(16));return i.join("")}e.exports={generateUuid:r,generateSpanId:o,generateTraceId:i}},{}],24:[function(t,e,n){function r(t,e){if(!o)return!1;if(t!==o)return!1;if(!e)return!0;if(!i)return!1;for(var n=i.split("."),r=e.split("."),a=0;a<r.length;a++)if(r[a]!==n[a])return!1;return!0}var o=null,i=null,a=/Version\/(\S+)\s+Safari/;if(navigator.userAgent){var c=navigator.userAgent,s=c.match(a);s&&c.indexOf("Chrome")===-1&&c.indexOf("Chromium")===-1&&(o="Safari",i=s[1])}e.exports={agent:o,version:i,match:r}},{}],25:[function(t,e,n){function r(t){function e(){t(a&&document[a]?document[a]:document[o]?"hidden":"visible")}"addEventListener"in document&&i&&document.addEventListener(i,e,!1)}e.exports=r;var o,i,a;"undefined"!=typeof document.hidden?(o="hidden",i="visibilitychange",a="visibilityState"):"undefined"!=typeof document.msHidden?(o="msHidden",i="msvisibilitychange"):"undefined"!=typeof document.webkitHidden&&(o="webkitHidden",i="webkitvisibilitychange",a="webkitVisibilityState")},{}],26:[function(t,e,n){function r(t,e){var n=[],r="",i=0;for(r in t)o.call(t,r)&&(n[i]=e(r,t[r]),i+=1);return n}var o=Object.prototype.hasOwnProperty;e.exports=r},{}],27:[function(t,e,n){function r(t,e,n){e||(e=0),"undefined"==typeof n&&(n=t?t.length:0);for(var r=-1,o=n-e||0,i=Array(o<0?0:o);++r<o;)i[r]=t[e+r];return i}e.exports=r},{}],28:[function(t,e,n){e.exports={exists:"undefined"!=typeof window.performance&&window.performance.timing&&"undefined"!=typeof window.performance.timing.navigationStart}},{}],ee:[function(t,e,n){function r(){}function o(t){function e(t){return t&&t instanceof r?t:t?s(t,c,i):i()}function n(n,r,o,i){if(!p.aborted||i){t&&t(n,r,o);for(var a=e(o),c=m(n),s=c.length,f=0;f<s;f++)c[f].apply(a,r);var d=u[y[n]];return d&&d.push([x,n,r,a]),a}}function l(t,e){g[t]=m(t).concat(e)}function h(t,e){var n=g[t];if(n)for(var r=0;r<n.length;r++)n[r]===e&&n.splice(r,1)}function m(t){return g[t]||[]}function v(t){return d[t]=d[t]||o(n)}function w(t,e){f(t,function(t,n){e=e||"feature",y[n]=e,e in u||(u[e]=[])})}var g={},y={},x={on:l,addEventListener:l,removeEventListener:h,emit:n,get:v,listeners:m,context:e,buffer:w,abort:a,aborted:!1};return x}function i(){return new r}function a(){(u.api||u.feature)&&(p.aborted=!0,u=p.backlog={})}var c="nr@context",s=t("gos"),f=t(26),u={},d={},p=e.exports=o();p.backlog=u},{}],gos:[function(t,e,n){function r(t,e,n){if(o.call(t,e))return t[e];var r=n();if(Object.defineProperty&&Object.keys)try{return Object.defineProperty(t,e,{value:r,writable:!0,enumerable:!1}),r}catch(i){}return t[e]=r,r}var o=Object.prototype.hasOwnProperty;e.exports=r},{}],handle:[function(t,e,n){function r(t,e,n,r){o.buffer([t],r),o.emit(t,e,n)}var o=t("ee").get("handle");e.exports=r,r.ee=o},{}],id:[function(t,e,n){function r(t){var e=typeof t;return!t||"object"!==e&&"function"!==e?-1:t===window?0:a(t,i,function(){return o++})}var o=1,i="nr@id",a=t("gos");e.exports=r},{}],loader:[function(t,e,n){function r(){if(!E++){var t=b.info=NREUM.info,e=l.getElementsByTagName("script")[0];if(setTimeout(u.abort,3e4),!(t&&t.licenseKey&&t.applicationID&&e))return u.abort();f(y,function(e,n){t[e]||(t[e]=n)});var n=a();s("mark",["onload",n+b.offset],null,"api"),s("timing",["load",n]);var r=l.createElement("script");r.src="https://"+t.agent,e.parentNode.insertBefore(r,e)}}function o(){"complete"===l.readyState&&i()}function i(){s("mark",["domContent",a()+b.offset],null,"api")}function a(){return R.exists&&performance.now?Math.round(performance.now()):(c=Math.max((new Date).getTime(),c))-b.offset}var c=(new Date).getTime(),s=t("handle"),f=t(26),u=t("ee"),d=t(24),p=window,l=p.document,h="addEventListener",m="attachEvent",v=p.XMLHttpRequest,w=v&&v.prototype;NREUM.o={ST:setTimeout,SI:p.setImmediate,CT:clearTimeout,XHR:v,REQ:p.Request,EV:p.Event,PR:p.Promise,MO:p.MutationObserver};var g=""+location,y={beacon:"bam.nr-data.net",errorBeacon:"bam.nr-data.net",agent:"js-agent.newrelic.com/nr-spa-1177.min.js"},x=v&&w&&w[h]&&!/CriOS/.test(navigator.userAgent),b=e.exports={offset:c,now:a,origin:g,features:{},xhrWrappable:x,userAgent:d};t(19),t(22),l[h]?(l[h]("DOMContentLoaded",i,!1),p[h]("load",r,!1)):(l[m]("onreadystatechange",o),p[m]("onload",r)),s("mark",["firstbyte",c],null,"api");var E=0,R=t(28)},{}],"wrap-function":[function(t,e,n){function r(t){return!(t&&t instanceof Function&&t.apply&&!t[a])}var o=t("ee"),i=t(27),a="nr@original",c=Object.prototype.hasOwnProperty,s=!1;e.exports=function(t,e){function n(t,e,n,o){function nrWrapper(){var r,a,c,s;try{a=this,r=i(arguments),c="function"==typeof n?n(r,a):n||{}}catch(f){p([f,"",[r,a,o],c])}u(e+"start",[r,a,o],c);try{return s=t.apply(a,r)}catch(d){throw u(e+"err",[r,a,d],c),d}finally{u(e+"end",[r,a,s],c)}}return r(t)?t:(e||(e=""),nrWrapper[a]=t,d(t,nrWrapper),nrWrapper)}function f(t,e,o,i){o||(o="");var a,c,s,f="-"===o.charAt(0);for(s=0;s<e.length;s++)c=e[s],a=t[c],r(a)||(t[c]=n(a,f?c+o:o,i,c))}function u(n,r,o){if(!s||e){var i=s;s=!0;try{t.emit(n,r,o,e)}catch(a){p([a,n,r,o])}s=i}}function d(t,e){if(Object.defineProperty&&Object.keys)try{var n=Object.keys(t);return n.forEach(function(n){Object.defineProperty(e,n,{get:function(){return t[n]},set:function(e){return t[n]=e,e}})}),e}catch(r){p([r])}for(var o in t)c.call(t,o)&&(e[o]=t[o]);return e}function p(e){try{t.emit("internal-error",e)}catch(n){}}return t||(t=o),n.inPlace=f,n.flag=a,n}},{}]},{},["loader",2,16,5,3,4]); ;NREUM.loader_config={accountID:"2095297",trustKey:"2038175",agentID:"916964291",licenseKey:"16e2192192",applicationID:"916964291"} ;NREUM.info={beacon:"bam.nr-data.net",errorBeacon:"bam.nr-data.net",licenseKey:"16e2192192",applicationID:"916964291",sa:1} </script> <script src="https://cdn.cookielaw.org/scripttemplates/otSDKStub.js" type="text/javascript" charset="UTF-8" data-domain-script="cadd58fe-2c94-41f7-8709-5a7176b7a852"></script> <script type="text/javascript"> function getCookie(name) { var value = "; " + document.cookie; var parts = value.split("; " + name + "="); if (parts.length == 2) { return true; } } function OptanonWrapper() { var optCookie = getCookie("OptanonAlertBoxClosed"); var isActiveCategory = "false"; var isFoundCookieBox = "false"; if(isActiveCategory == 'false' && isFoundCookieBox == 'false' && optCookie) { OneTrust.InsertScript('/pb-assets/adobe/prod/adobedtm-1616606406233.js', 'head', null, null, '2'); } } </script> <noscript> <style>.requiresJS { display: none } .dartAd { display: block !important }</style> </noscript> <script type="text/javascript" src="/wro/nnkn~selected-legacy.js"></script> <link rel="stylesheet" type="text/css" href="/wro/nnkn~selected-legacy.css"/> <link rel="stylesheet" href="https://fonts.googleapis.com/css?family=Open+Sans"/> <script>window.MSInputMethodContext && document.documentMode && document.write('<script src="https://cdn.jsdelivr.net/gh/nuxodin/ie11CustomProperties@4.1.0/ie11CustomProperties.min.js"><\x2fscript>');</script><link rel="stylesheet" href="/products/marlin/ha/releasedAssets/css/build-45520a2122a8fee68553.css"/><link rel="stylesheet" href="/products/marlin/ha/releasedAssets/css/print-45520a2122a8fee68553.css" media="print"/><link rel="stylesheet" href="/products/marlin/ha/releasedAssets/css/themes/theme-jcyt.css"/> <script class="optanon-category-4" type="text/plain" async src="https://www.youtube.com/iframe_api"></script>  <meta http-equiv="X-UA-Compatible" content="IE=edge"> </head> <body class="pb-ui"> <div class="skip"> <a href="#page-body-id" id="skipNavigationLink" title="Skip to Main Content" tabindex="0" class="skipToContent">Skip to Main Content</a> <a href="#mega-menu-nav" id="skipToMainMenu" title="Skip to Main Menu" tabindex="0" class="skipToContent">Skip to Main Menu</a> </div> <div id="pb-page-content" data-ng-non-bindable> <div data-pb-dropzone="main" data-pb-dropzone-name="Main"> <div data-widget-def="ux3-layout-widget" data-widget-id="54cf691d-1d44-49ee-922c-5ca55dc1d4af" class="ux3"> <div class="jcyt"> <div data-widget-id="54cf691d-1d44-49ee-922c-5ca55dc1d4af" data-widget-name="ux3-layout-widget"><div> <div id="6ee85045-2441-4b5c-8a4b-4c078d548375" class="widget loginPopup none widget-none widget-compact-all"><div class="wrapped"><div class="widget-body body body-none body-compact-all"><div role="dialog" aria-modal="true" aria-label="Login" class="popup login-popup hidden"><div class="content"><a href="#" aria-label="Close login popup" title="Close login popup" role="button" class="close"><i class="icon-close_thin"></i></a><h2 class="login-title">Login to your account</h2><div class="login-form"><p tabindex="-1" class="message error"></p><form action="/action/doLogin?redirectUri=https%3A%2F%2Fwww.isct-cytotherapy.org%2Farticle%2FS1465-3249%2823%2900064-6%2Ffulltext" method="post"><input type="hidden" name="redirectUri" value="https://www.isct-cytotherapy.org/article/S1465-3249(23)00064-6/fulltext"/><input type="hidden" name="referer" value="/article/S1465-3249(23)00064-6/fulltext"/><input type="hidden" name="ecommRedirect"/><input type="hidden" name="code" value="jcyt-site"/><input type="hidden" name="UX3LoginWidget" value="true"/><input type="hidden" name="isPopup" value="true"/><div class="input-group login-input--wrapper"><div class="label"><label for="login">Email/Username</label></div><input id="login" type="text" name="login" value="" size="15" class="login"/><div role="alert" class="error-hint js--hidden"><div class="error-hint__text"><div class="error-text">Your email address is a required field.</div><div class="email-example">E.g., j.smith@mail.com</div></div></div></div><div class="input-group login-input--wrapper"><div class="label"><label for="password">Password</label></div><input id="password" type="password" name="password" value="" autocomplete="off" class="password"/><a href="#" class="login__field__action js-show-password">Show</a><div role="alert" class="error-hint js--hidden"><span class="error-hint__text">Your password is a required field.</span></div><div class="actions"><a href="https://www.isct-cytotherapy.org/action/requestResetPassword" class="link show-request-reset-password">Forgot password?</a></div></div><div class="remember"><input type="checkbox" name="savePassword" id="6ee85045-2441-4b5c-8a4b-4c078d548375-remember" value="1" checked="checked"/><label for="6ee85045-2441-4b5c-8a4b-4c078d548375-remember">Remember me</label></div><div class="submit"><input type="submit" name="submit" value="Log in" class="button submit primary"/></div></form></div><div class="create-account"><div>Don’t have an account?</div><a href="/action/registration?redirectUri=https%3A%2F%2Fwww.isct-cytotherapy.org%2Farticle%2FS1465-3249%2823%2900064-6%2Ffulltext" class="show-registration">Create a Free Account</a></div></div></div></div></div></div> <div role="dialog" aria-modal="true" aria-label="Reset password" class="popup top-drawer request-reset-password-drawer hidden"><div class="content"><a href="#" aria-label="Close reset password popup" title="Close reset password popup" role="button" class="close"><i class="icon-close_thin"></i></a><div class="request-reset"><div class="form"><p class="sub">If you don't remember your password, you can reset it by entering your email address and clicking the Reset Password button. You will then receive an email that contains a secure link for resetting your password</p><div tabindex="-1" class="message error"></div><form action="/action/requestResetPassword" method="post" class="request-reset-password-form"><input type="hidden" name="platform"/><input type="hidden" name="requestResetPassword" value="true"/><input type="hidden" name="codeSite" value="jcyt-site"/><div class="input-group"><div class="label"><label for="reset-password-email">Email*</label></div><input id="reset-password-email" type="text" name="email" value="" size="15" class="email"/></div><div class="submit"><input type="submit" name="submit" value="Submit" disabled="disabled" class="button primary submit"/></div></form></div><div class="success-template hidden"><p>If the address matches a valid account an email will be sent to __email__ with instructions for resetting your password</p></div></div><div class="request-reset-cancel"><a href="#" aria-label="Close reset password popup" title="Close reset password popup" class="cancel">Cancel</a></div></div></div> <div class="ux3-ads"> <div class="pb-ad">    <div id="gpt-Variables" data-adfile="JBS"> <input type="hidden" id="gptSite" value="jcyt"> <input type="hidden" id="gptLoggedIn" value="no"> <input type="hidden" id="gptAccessType" value="ae:ANON_GUEST|ae:ANON_GUEST"> </div> <div id="gpt-Interscroller" class="gpt-InScrollBox" style="display:none;"> <div class="gpt-InScrollLabel">ADVERTISEMENT</div> <div class="gpt-InScrollContainer"> <div class="gpt-InScrollWrapper"> <div class="gpt-InScrollInner"> <div class="gpt-adinterscroller" data-adsize="interscroller"></div> </div> </div> </div> <div class="gpt-InScrollLabel">SCROLL TO CONTINUE WITH CONTENT</div> </div> <div id="gpt-DebugDiv" class="gpt-DebugDiv" style="display:none;"> <div style="width: 100%; display: table;"> <div style="display: table-row"> <div style="width: 200px; display: table-cell;"> <button class="gpt-DebugBtn" onclick="gpt_ShowConsole()">Open GPT Console</button><br /> <button id="gpt_GrapeShotDebugBtn" class="gpt-DebugBtn" onclick="gpt_GrapeShotDebug();">Open Oracle Keywords</button><br /> <br /> <button class="gpt-DebugBtn" onclick="gpt_LoadDebugValues()">Refresh Values</button> </div> <div style="display: table-cell;"> <table class="gpt-DebugTable"> <thead> <tr> <th>Property</th> <th>Value</th> </tr> </thead> <tbody> <tr><td class="gpt-DebugTitle">Status</td><td><div class="gptStatus_Debug"></div></td></tr> <tr><td class="gpt-DebugTitle">Version</td><td><div class="gptVersion_Debug"></div></td></tr> <tr><td class="gpt-DebugTitle">Ad File</td><td><div class="gptAdFile_Debug"></div></td></tr> <tr><td class="gpt-DebugTitle">Disable Ads Flag</td><td><div class="gptDisableAds_Debug"></div></td></tr> <tr><td class="gpt-DebugTitle">Environment</td><td><div class="gptTestENV_Debug"></div></td></tr> <tr><td class="gpt-DebugTitle">Moat Init</td><td><div class="gptMoatInit_Debug"></div></td></tr> <tr><td class="gpt-DebugTitle">Moat Ready</td><td><div class="gptMoatReady_Debug"></div></td></tr> <tr><td class="gpt-DebugTitle">Contextual Ready</td><td><div class="gptContextualReady_Debug"></div></td></tr> <tr><td class="gpt-DebugTitle">Contextual URL</td><td><div class="gptContextualURL_Debug"></div></td></tr> <tr><td class="gpt-DebugTitle">Contextual Initial Segments</td><td><div class="gptContextualInit_Debug"></div></td></tr> <tr><td class="gpt-DebugTitle">Contextual Used Segments</td><td><div class="gptContextualResult_Debug"></div></td></tr> <tr><td class="gpt-DebugTitle">AdUnit</td><td><div class="gptSite_Debug"></div></td></tr> <tr><td class="gpt-DebugTitle">SubAdUnit</td><td><div class="gptPage_Debug"></div></td></tr> <tr><td class="gpt-DebugTitle">Custom Targeting</td><td><div class="gptCustomTargeting_Debug"></div></td></tr> <tr><td class="gpt-DebugTitle">Ad Events</td><td><div class="gptEvent_Debug"></div></td></tr> <tr><td class="gpt-DebugTitle">Invalid Ad Sizes</td><td><div class="gptInvalidAdSize_Debug"></div></td></tr> </tbody> </table> </div> </div> </div> </div> <style type="text/css"> .gpt-DebugBtn { display: inline-block; text-align: center; text-decoration: none; margin: 2px 0; border: solid 1px #122b40; border-radius: 0.4em; padding: 0.5em 1em; color: #ffffff; background-color: #204d74; font-weight: normal; font-size: 12px; } .gpt-DebugDiv { margin: 5px; } .gpt-DebugTitle { font-weight: bold; } .gpt-DebugTable { border: 1px solid #dddddd; border-collapse: collapse; margin: 5px; font-size: 0.9em; font-family: sans-serif; min-width: 400px; margin-bottom: 25px; } .gpt-DebugTable td:first-child { padding: 5px; } .gpt-DebugTable thead tr th { background-color: #d9edf7; color: #ffffff; text-align: left; padding: 5px; border-bottom: 2px solid #204d74; } .gpt-DebugTable th, .gpt-DebugTable td { padding: 5px; } .gpt-DebugTable tbody tr { border-bottom: 1px solid #dddddd; } .gpt-DebugTable tbody tr:nth-of-type(even) { background-color: #f3f3f3; } .gpt-DebugTable tbody tr:last-of-type { border-bottom: 2px solid #204d74; } .gpt-InScrollLabel { background-color: rgb(0, 0, 0); color: rgb(255, 255, 255); position: relative; max-width: 100vw; left: 50%; right: 50%; margin-left: -50vw; margin-right: -50vw; padding: 0; text-align: center; width: 100vw !important; font-size: 10px; } .gpt-InScrollBox { height: 100vh !important; width: 100vw; cursor: pointer; max-width: 100vw; position: relative; left: 50%; right: 50%; margin-left: -50vw; margin-right: -50vw; margin-bottom: 50px; padding-top: 5px; padding-bottom: 5px; z-index: 10001; background-color: white; } .gpt-InScrollBox .gpt-InScrollContainer { height: 95vh !important; position: relative; } .gpt-InScrollBox .gpt-InScrollWrapper { position: absolute !important; top: 0 !important; left: 0; width: 100%; height: 95vh !important; border: 0 !important; margin: 0 !important; padding: 0 !important; clip: rect(0, auto, auto, 0) !important; -webkit-clip-path: polygon(0px 0px, 100% 0px, 100% 100%, 0px 100%) !important; clip-path: polygon(0px 0px, 100% 0px, 100% 100%, 0px 100%) !important; } .gpt-InScrollBox .gpt-InScrollInner { position: fixed !important; top: 0 !important; left: 0 !important; bottom: 0; margin: auto; width: 100vw; height: 95vh; -webkit-transform: translateZ(0) !important; display: -webkit-box; display: -ms-flexbox; display: flex; -webkit-box-orient: vertical; -webkit-box-direction: normal; -ms-flex-direction: column; flex-direction: column; -webkit-box-align: center; -ms-flex-align: center; align-items: center; -webkit-box-pack: center; -ms-flex-pack: center; justify-content: center; text-align: center; } </style> <script class="optanon-category-4" type="text/plain"> //-------------------------------------------------------------------------- var gpt_Version = '04072023'; var gpt_AdFile = $('#gpt-Variables').data('adfile'); var gpt_MaxMOATInitAttempts = 11; var gpt_MaxMOATReadyAttempts = 11; var gpt_MaxContextualReadyAttempts = 21; var gpt_MOATInitAttempts = 0; var gpt_MOATReadyAttempts = 0; var gpt_ContextualReadyAttempts = 0; var gpt_IsProd = true; var gpt_StartTime; var gs_channels = 'DEFAULT'; var gpt_ContextualReady = false; var gpt_ContextualURL = 'Not enabled outside of Production'; var gpt_DisableAdsFlagFound = false; var gptEvent_Debug = ''; var gptCustomTargeting_Debug = ''; var gptSite_Debug = ""; var gptPage_Debug = ""; var gptContextualEnabled = false; var gptContextualResult_Debug = ''; var gptContextualInit_Debug = ''; var gptContextualURL_Debug = ''; var gptContextualReady_Debug = ''; var gptMoatReady_Debug = ''; var gptMoatInit_Debug = ''; var gptTestENV_Debug = ''; var gptDisableAds_Debug = ''; var gptStatus_Debug = 'GPT Still Loading - Refresh Values'; var gptInvalidAdSize_Debug = ''; //-------------------------------------------------------------------------- $(document).ready(function () { //Check to see if we are on a development env gpt_CheckEnvironment(); if (!gpt_DisableAdsFlagFound) { gpt_StartTime = new Date(); if (gpt_AdFile !== "PU") { //Once the dom has loaded, begin the process to init the ads. gpt_InitScripts(); gpt_CheckForMOATInit(); } } }); </script> <script type="text/javascript"> function gpt_CheckEnvironment() { if ($('#gptDisableAds').length > 0) { gptDisableAds_Debug = 'Flag Detected - Ads Disabled'; gpt_DisableAdsFlagFound = true; } else { gptDisableAds_Debug = 'Ads Enabled'; gpt_DisableAdsFlagFound = false; } switch (gpt_AdFile) { case 'PU': gptContextualEnabled = true; if ($("#Environment").val() !== "Prod") { gpt_IsProd = false; gptTestENV_Debug = 'Test Environment Detected'; } else { gptTestENV_Debug = 'Production Environment Detected'; } break; case 'JBS': case 'LANCET': gptContextualEnabled = true; if ($(".gpt-ad").length > 0) { //Other ads exist, allow the Prestitial $(document.body).append("<div class='gpt-ad' data-adsize='prestitial'></div>"); } if (window.location.hostname.toLowerCase().indexOf('.literatumonline.') >= 0) { gpt_IsProd = false; gptTestENV_Debug = 'Test Environment Detected'; } else { gptTestENV_Debug = 'Production Environment Detected'; } break; default: //Cell gptContextualEnabled = false; if (window.location.hostname.toLowerCase().indexOf('.literatumonline.') >= 0) { gpt_IsProd = false; gptTestENV_Debug = 'Test Environment Detected'; } else { gptTestENV_Debug = 'Production Environment Detected'; } break; } } //-------------------------------------------------------------------------- function gpt_GetNonCMEArticle() { var url; $('.articleCitation').each(function (i, obj) { if ($(obj).find('.toc__item__detials').length > 0) { var itemDetails = $(obj).first().find('.toc__item__detials'); var cmeFound = 0; if (cmeFound == 0) { cmeFound = $(itemDetails).find("img[title~='CME']").length; } if (cmeFound == 0) { cmeFound = $(itemDetails).find("img[title~='(CME)']").length; } if (cmeFound == 0) { cmeFound = $(itemDetails).find("img[title~='Education']").length; } if (cmeFound == 0) { cmeFound = $(itemDetails).find("img[title~='education']").length; } if (cmeFound == 0) { var itemLink = $(itemDetails).first().find('.toc__item__title'); var linkCount = $(itemLink).first().find("a:contains('CME')").length; if (linkCount == 0) { url = $(itemLink).first().find('a').attr('href'); return false; //Found a URL, break the loop } } } }); return url; } //-------------------------------------------------------------------------- function gpt_GetElapsedTime() { var endTime = new Date(); var timeDiff = endTime - gpt_StartTime; //in ms // strip the ms timeDiff /= 1000; // get seconds return seconds = Math.round(timeDiff) + " seconds"; } //-------------------------------------------------------------------------- function gpt_CheckSSC() { //Check for ScreenShot Client var gpt_SSC = gpt_GetQuerystring('gpt_ssc', ''); if (gpt_SSC == '1') { //it's the ScreenShotClient, disable MOAT IVT Detection $('#gpt-Variables').append('<input type="hidden" id="gptm_data">'); $('#gptm_data').val(0); gpt_Target("m_data"); } } //-------------------------------------------------------------------------- function gpt_LocalSS(adTypeId) { window.scrollTo(0, 0); gpt_Sleep(1000); gpt_ScrollToAd(adTypeId); gpt_PreTearsheet(adTypeId); } //-------------------------------------------------------------------------- function gpt_InitScripts() { if (gpt_AdFile == "PU") { if (gpt_IsProd) { gpt_ContextualURL = gpt_CheckForNULL($('#canonicalurl').val()); if (gpt_ContextualURL === null) { gpt_ContextualURL = window.location.href.split('?')[0].split('#')[0]; } else { gpt_ContextualURL = window.location.origin + gpt_ContextualURL; } var useSSL = 'https:' == document.location.protocol; var gs = document.createElement('script'); gs.async = true; gs.type = 'text/javascript'; gs.src = (useSSL ? 'https:' : 'http:') + '//elsevier.gscontxt.net/multizone/channels.cgi?url=' + encodeURIComponent(gpt_ContextualURL); gs.onload = function () { gpt_ContextualReady = true; }; document.head.appendChild(gs); } } else { //JBS-Cell-Lancet var useSSL = 'https:' == document.location.protocol; var gads = document.createElement('script'); gads.async = true; gads.type = 'text/javascript'; gads.src = (useSSL ? 'https:' : 'http:') + '//securepubads.g.doubleclick.net/tag/js/gpt.js'; document.head.appendChild(gads); if (gpt_IsProd && gptContextualEnabled) { gpt_ContextualURL = window.location.href.split('?')[0].split('#')[0]; var gs = document.createElement('script'); gs.async = true; gs.type = 'text/javascript'; gs.src = (useSSL ? 'https:' : 'http:') + '//elsevier.gscontxt.net/multizone/channels.cgi?url=' + encodeURIComponent(gpt_ContextualURL); gs.onload = function () { gpt_ContextualReady = true; }; document.head.appendChild(gs); } var elsevierMoatHeader = document.createElement('link'); elsevierMoatHeader.rel = 'preload'; elsevierMoatHeader.as = 'script'; elsevierMoatHeader.src = (useSSL ? 'https:' : 'http:') + '//z.moatads.com/elsevierheader150204004183/moatheader.js'; document.head.appendChild(elsevierMoatHeader); var elsevierMoatAds = document.createElement('link'); elsevierMoatAds.rel = 'preconnect'; elsevierMoatAds.src = (useSSL ? 'https:' : 'http:') + '//mb.moatads.com'; document.head.appendChild(elsevierMoatAds); var moatHeader = document.createElement('script'); moatHeader.async = true; gads.type = 'text/javascript'; moatHeader.src = (useSSL ? 'https:' : 'http:') + '//z.moatads.com/elsevierheader150204004183/moatheader.js'; document.head.appendChild(moatHeader); } } //-------------------------------------------------------------------------- async function gpt_CheckForMOATInit() { //Check every 1/10 of a second until MOAT is Loaded or 1 second timeout if (gpt_MOATInitAttempts < gpt_MaxMOATInitAttempts) { gpt_MOATInitAttempts += 1; if (typeof window.moatPrebidApi === "object") { //MOAT LOADED gptMoatInit_Debug = '0.0' + gpt_MOATInitAttempts + ' seconds'; gpt_CheckForMOATReady(); } else { setTimeout(() => { gpt_CheckForMOATInit(); }, 100); } } else { //TIMEOUT: MOAT Not LOADED gptMoatInit_Debug = 'Timeout Expired'; var googletag = googletag || {}; googletag.cmd = googletag.cmd || []; gpt_CheckForContextualReady(); } } //-------------------------------------------------------------------------- function gpt_CheckForMOATReady() { //Check every 1/10 of a second until MOAT is Ready or 1 second timeout if (gpt_MOATReadyAttempts < gpt_MaxMOATReadyAttempts) { gpt_MOATReadyAttempts += 1; if (window.moatPrebidApi.safetyDataAvailable()) { //MOAT Ready gptMoatReady_Debug = '0.0' + gpt_MOATReadyAttempts + " seconds"; gpt_CheckForContextualReady(); } else { setTimeout(() => { gpt_CheckForMOATReady(); }, 100); } } else { //TIMEOUT: MOAT Not Ready gptMoatReady_Debug = 'Timeout Expired'; gpt_CheckForContextualReady(); } } //-------------------------------------------------------------------------- function gpt_CheckForContextualReady() { //Check every 1/10 of a second until Contextual is Ready or 2 second timeout if (gpt_IsProd && gptContextualEnabled) { //Enabled if (gpt_ContextualReadyAttempts < gpt_MaxContextualReadyAttempts) { gpt_ContextualReadyAttempts += 1; if (gpt_ContextualReady) { //Contextual Ready gptContextualURL_Debug = gpt_ContextualURL; gptContextualReady_Debug = '0.0' + gpt_ContextualReadyAttempts + " seconds"; gptContextualInit_Debug = gs_channels; gpt_InitAds(); } else { setTimeout(() => { gpt_CheckForContextualReady(); }, 100); } } else { //LOG TIMEOUT error //REMOVE FOR NOW (SHOULD LOG TO A DIFF LOCATION) //TIMEOUT: Contextual Not Ready $('#gpt_GrapeShotDebugBtn').remove(); gptContextualURL_Debug = gpt_ContextualURL; gptContextualReady_Debug = 'Timeout Expired'; gptContextualInit_Debug = ""; gpt_InitAds(); } } else { //Not Enabled $('#gpt_GrapeShotDebugBtn').remove(); switch (gpt_AdFile) { case 'PU': case 'LANCET': case 'JBS': gptContextualURL_Debug = 'Not enabled outside of Production'; gptContextualReady_Debug = 'Not enabled outside of Production'; gptContextualInit_Debug = 'Not enabled outside of Production'; break; case "CELLJOURNAL": case "CELLBUCKET": gptContextualReady_Debug = 'Not enabled on Cell'; gptContextualInit_Debug = 'Not enabled on Cell'; gptContextualURL_Debug = 'Not enabled on Cell'; break; } gpt_InitAds(); } } //-------------------------------------------------------------------------- function GPT_GetPageByURL() { var host = window.location.host.toLocaleLowerCase() var localpath = window.location.pathname.toLocaleLowerCase(); ///Check for Cell.com if (host.indexOf('cell.com') >= 0) { return null; } ///Check for Cell.com (marlin-stag) if (host.indexOf('www-cell-com') >= 0) { return null; } ///Check for Lancet if (host.indexOf('thelancet') >= 0) { return null; } if (localpath.indexOf('/article/') >= 0) { return 'article.fulltext'; } if (localpath.indexOf('/action/dosearch') >= 0) { return 'search.searchResults'; } if (localpath.indexOf('/content/') >= 0) { return 'periodical.editorial'; } return 'periodical.home'; } //-------------------------------------------------------------------------- function gpt_CheckForNULL(x, valueifnull) { if (typeof valueifnull == "undefined") { valueifnull = null; } if (typeof x == 'undefined') { return valueifnull; } if (x == null) { return valueifnull; } if (x == "null") { return valueifnull; } if ($.trim(x) == '') { return valueifnull; } return x; } //-------------------------------------------------------------------------- function gpt_GetAdditionalTargeting() { //adds page level targeting of custom variables //the id (minus gpt) and the value will be used as a key-value pair //eg: <input type="hidden" id="gptissuepii" value="x" class="gpt-Target"> //eg: target issuepii=x $(".gpt-Target").each(function (index) { var gptTargetId = $(this).attr('id'); gptTargetId = gptTargetId.replace('gpt', '').toLowerCase(); if (gptTargetId !== '') { gpt_Target(gptTargetId); } }) } //-------------------------------------------------------------------------- function gpt_GetQuerystring(key, default_) { //function to read querystring variables if (default_ === null) default_ = ''; key = key.replace(/[\[]/, "\\\[").replace(/[\]]/, "\\\]"); var regex = new RegExp("[\\?&]" + key + "=([^&#]*)"); var qs = regex.exec(window.location.href); if (qs === null) return default_; else return qs[1]; } //-------------------------------------------------------------------------- function gpt_GetDFPTestId() { //Get any request for a test id from querystring and set custom targeting parameter var gptDFPTestId = gpt_GetQuerystring('dfptestid', ''); if (gptDFPTestId !== '') { $('#gpt-Variables').append('<input type="hidden" id="gptDFPTestId">'); $('#gptDFPTestId').val(gptDFPTestId); gpt_Target("DFPTestId"); } } //-------------------------------------------------------------------------- function gpt_Target(targetName) { //Set page level target if value is found if ($('#gpt' + targetName).length > 0) { var targetValue = $('#gpt' + targetName).val(); if (targetValue !== '') { targetValue = targetValue.replace(/[^-a-z0-9]/ig, ''); //Only Allow a-z, 0-9 googletag.pubads().setTargeting(targetName.toLowerCase(), targetValue.toLowerCase()); gptCustomTargeting_Debug = gptCustomTargeting_Debug + targetName.toLowerCase() + ' = ' + targetValue.toLowerCase() + '<br>'; } } } //-------------------------------------------------------------------------- function gpt_TargetAccessType() { var currentAccessType = $('#gptAccessType').val(); if (typeof currentAccessType == "undefined") { currentAccessType = ""; } if (currentAccessType.indexOf('ANON_IP') >= 0) { googletag.pubads().setTargeting("loggedin", "yes"); } else { gpt_Target("LoggedIn"); } } //-------------------------------------------------------------------------- async function gpt_PreTearsheet(adTypeId) { if (typeof adTypeId === "undefined") { adTypeId = 0; } //Remove Elsevier Cookie Policy Notice if ($("#onetrust-consent-sdk").length > 0) { $("#onetrust-consent-sdk").remove(); } //Mobile Nav $('#skip').remove(); $('#skipNavigationLink').remove(); //JBS Modals if ($('.leadinModal').length > 0) { $('.leadinModal').remove(); } if ($('.leadinModal').length > 0) { $('.leadinModal').remove(); } if ($('.usabilla__overlay').length > 0) { $('.usabilla__overlay').remove(); } //Pendo if ($('._pendo-step-container').length > 0) { $('._pendo-step-container').remove(); } if ($('._pendo-guide-tt_').length > 0) { $('._pendo-guide-tt_').remove(); } if ($('._pendo-image').length > 0) { $('._pendo-image').remove(); } if ($('._pendo-badge-image').length > 0) { $('._pendo-badge-image').remove(); } switch (gpt_AdFile) { case "CELLJOURNAL": case "CELLBUCKET": //Mobile Bug Fix on Cell if (parseInt(adTypeId) == 5) { $('.widget-horizontalAd').css('position', 'static'); $('.body-horizontalAd').css('display', 'block'); } break; case "JBS": case "LANCET": objLeaderboard = ".container-leaderboard"; offset = 53; switch (parseInt(adTypeId)) { case 3: //MPU case 4: //SkyScraper //BUGFIX: Show Sidebar ad for JBS //skyscraper & mpu if ($('.widget-verticalAd').length > 0) { $('.widget-verticalAd').css('display', 'block'); } $('#backgroundLayer').css('display', 'none'); //Hide any Prestitial break; case 6: //Prestitial $('#backgroundLayer').css('display', 'block'); break; default: $('#backgroundLayer').css('display', 'none'); //Hide any Prestitial break; } break; } } //-------------------------------------------------------------------------- function gpt_Sleep(ms) { return new Promise(resolve => setTimeout(resolve, ms)); } //-------------------------------------------------------------------------- async function gpt_ScrollToAd(adTypeId) { if (typeof adTypeId === "undefined") { adTypeId = 0; } var adId = ""; var offset = 0; var objLeaderboard = ""; var gpt_ScrollToAd = true; switch (gpt_AdFile) { case "PU": //PracticeUpdate var hideOtherAds = true; $('#modalPrestitial').modal('hide'); $('.jumbotron-welcome').hide(); objLeaderboard = ".container-leaderboard"; offset = 53; switch (parseInt(adTypeId)) { case 2: //LeaderBoard, no Scroll Needed gpt_ScrollToAd = false; adId = "adSlot1"; break; case 3: //MPU adId = "adSlot2"; break; case 4: //SkyScraper adId = "adSlot3"; $('.most-read').hide(); break; case 5: //Mobile, no Scroll Needed gpt_ScrollToAd = false; adId = "adSlot1"; break; case 6: //Interstitial gpt_ScrollToAd = false; adId = "adSlot15"; await gpt_Sleep(1000); $(objLeaderboard).hide(); $('#modalPrestitial').unbind(); $('#modalPrestitial').modal(); break; case 7: //Native Ad break; case 10: //Master Companion hideOtherAds = false; gpt_ScrollToAd = false; break; default: //Unknown Ad Type gpt_ScrollToAd = false; adId = "adSlot1"; break; } if (hideOtherAds) { //Hide all other ads $('.ad-container').each(function (i, obj) { if (this.id !== adId) { var tempParent = this.id; tempParent = tempParent.replace("adSlot", "adParent"); $("#" + tempParent).addClass('hide'); } }); } break; case "JBS": objLeaderboard = ".js__adToHide"; offset = 80; switch (parseInt(adTypeId)) { case 2: //Leaderboard gpt_ScrollToAd = false; $(".widget-verticalAd").hide(); break; case 5: //Mobile //Scroll to Top gpt_ScrollToAd = false; break; case 3: //MPU case 4: //SkyScraper $(objLeaderboard).hide(); adId = $('.gpt-ad-defined[data-adsize="sidebar"').attr('id'); break; case 10: //MasterCompanion gpt_ScrollToAd = false; break; case 13: //Phone - Portrait case 14: //Phone - Landscape $(objLeaderboard).hide(); offset = 60; adId = 'gpt-Interscroller'; gpt_ScrollToAd = true; break; default: //Unknown Ad Type gpt_ScrollToAd = false; break; } break; case "CELLJOURNAL": case "CELLBUCKET": objLeaderboard = ".js__adToHide"; offset = 260; switch (parseInt(adTypeId)) { case 2: //Leaderboard gpt_ScrollToAd = false; $('.body-verticalAd').hide(); break; case 5: //Mobile //Scroll to Top gpt_ScrollToAd = false; break; case 3: //MPU case 4: //SkyScraper $(objLeaderboard).hide(); adId = $('.gpt-ad-defined[data-adsize="boombox"').attr('id'); break; case 10: //MasterCompanion gpt_ScrollToAd = false; break; default: //Unknown Ad Type gpt_ScrollToAd = false; break; } //Hide the second ad if found var tCount = 0; $(".widget.literatumAd.none.GPT-ad-placeholder.widget-horizontalAd.widget-compact-all").each(function (index) { tCount += 1; if (tCount !== 1) { $(this).hide(); } }); break; case "LANCET": objLeaderboard = ".js__adToHide"; offset = 80; switch (parseInt(adTypeId)) { case 2: //Leaderboard gpt_ScrollToAd = false; $('.body-verticalAd').hide(); break; case 5: //Mobile //Scroll to Top gpt_ScrollToAd = false; break; case 3: //MPU case 4: //SkyScraper $(objLeaderboard).hide(); adId = $('.gpt-ad-defined[data-adsize="skyscraper"').attr('id'); break; case 10: //MasterCompanion gpt_ScrollToAd = false; break; default: //Unknown Ad Type gpt_ScrollToAd = false; break; } break; } //Scroll to Top var gpt_container = $("html,body"); gpt_container.animate({ scrollTop: 0, scrollLeft: 0 }); if (gpt_ScrollToAd) { //If Adexists, scroll to it var gpt_scrollTo = $('#' + adId); if (gpt_scrollTo.length > 0) { //Scroll to the Ad var gpt_topPosition = gpt_scrollTo.offset().top - gpt_container.offset().top + gpt_container.scrollTop(); if (gpt_topPosition > 0) { gpt_container.animate({ scrollTop: gpt_topPosition, scrollLeft: 0 }); if (gpt_topPosition - offset > 0 && offset > 0) { gpt_container.animate({ scrollTop: gpt_topPosition - offset, scrollLeft: 0 }); } } } } } //-------------------------------------------------------------------------- async function gpt_CheckForCookiePolicy() { var returnVal = false; if ($('#onetrust-accept-btn-handler').length > 0) { $('#onetrust-accept-btn-handler').click(); returnVal = true; } return returnVal; } //-------------------------------------------------------------------------- function gpt_InitAds() { var gpt_ResponsiveHomepage = false; switch (gpt_AdFile) { case "JBS": case "CELLJOURNAL": case "CELLBUCKET": //Responsive Check if ($('#hdrHomeBrand').length > 0) { gpt_ResponsiveHomepage = true; } break; } //InterScroller Check if (gpt_AdFile === "JBS") { var gpt_InterScrollerEnabled = false; var gpt_InterScrollerInsertObj; if ($("#articleHeader").length > 0) { //It's an article Page if ($('.article__sections > section').length > 0) { gpt_InterScrollerEnabled = true; gpt_InterScrollerInsertObj = $(".article__sections > section"); } } else { if ($('.toc__section').length > 0) { //It's a TOC Page gpt_InterScrollerEnabled = true; gpt_InterScrollerInsertObj = $(".toc__section").first(); } } //Add the Interscroller if (gpt_InterScrollerEnabled) { gpt_InterScrollerInsertObj.first().append($("#gpt-Interscroller").clone()); $("#gpt-Interscroller").remove(); $(".gpt-adinterscroller").addClass("gpt-ad"); } } googletag.cmd.push(function () { var gptBoomBoxSizeMapping; var gptFluidMapping; var gptHomePageSidebarMapping; var gptCellHomePageSidebarMapping; var gptInterscrollerMapping; var gptLeaderboardSizeMapping; var gptMobileSizeMapping; var gptPrestitialMapping; var gptRectangleShortSizeMapping; var gptRectangleSizeMapping; var gptSideBarSizeMapping; var gptTallSizeMapping; var gptWideSizeMapping; var gptWideRectangleSizeMapping; //*********************************************** //Start Define Size mapping based on client Viewport //*********************************************** if (gpt_AdFile === 'PU') { gptTallSizeMapping = googletag.sizeMapping(). addSize([992, 0], [[300, 600], [160, 600], [120, 600]]). addSize([0, 0], []). build(); gptRectangleSizeMapping = googletag.sizeMapping(). addSize([992, 0], [[300, 250]]). addSize([0, 0], []). build(); gptRectangleShortSizeMapping = googletag.sizeMapping(). addSize([992, 0], [[300, 250], [320, 50], [300, 50]]). addSize([0, 0], [[300, 250], [320, 50], [300, 50]]). build(); gptWideSizeMapping = googletag.sizeMapping(). addSize([992, 0], [[728, 90]]). addSize([760, 0], [[728, 90], [320, 50], [300, 50]]). addSize([0, 0], [[320, 50], [300, 50]]). build(); gptWideRectangleSizeMapping = googletag.sizeMapping(). addSize([992, 0], []). addSize([760, 0], [[320, 50], [300, 50], [300, 250]]). addSize([0, 0], [[320, 50], [300, 50], [300, 250]]). build(); gptMobileSizeMapping = googletag.sizeMapping(). addSize([0, 0], [[320, 50], [300, 50]]). build(); gptFluidMapping = googletag.sizeMapping(). addSize([0, 0], ['fluid']). build(); gptPrestitialMapping = googletag.sizeMapping(). addSize([760, 0], [[1, 1]]). build(); } else { //JBS-CELL-LANCET gptLeaderboardSizeMapping = googletag.sizeMapping(). addSize([992, 0], [[728, 90]]). // Desktop addSize([768, 0], [[728, 90]]). // Tablet Landscape addSize([0, 0], [[320, 50], [300, 50]]). // Phone & Tablet Portrait build(); gptHomePageSidebarMapping = googletag.sizeMapping(). addSize([2090, 795], [[300, 600], [300, 250], [160, 600], [120, 600]]). addSize([1910, 795], [[160, 600], [120, 600]]). addSize([0, 0], []). build(); gptCellHomePageSidebarMapping = googletag.sizeMapping(). addSize([2090, 795], [[300, 600], [300, 250], [336, 280], [160, 600], [120, 600]]). addSize([1910, 795], [[160, 600], [120, 600]]). addSize([0, 0], []). build(); gptSideBarSizeMapping = googletag.sizeMapping(). addSize([1140, 795], [[300, 600], [160, 600], [120, 600], [300, 250]]). // SkyScraper - Desktop (Require min 630 vertical) addSize([1140, 445], [[300, 250]]). // BoomBox Fall Back - Desktop (Require min 280 vertical) addSize([0, 0], []). // Phone build(); gptBoomBoxSizeMapping = googletag.sizeMapping(). addSize([768, 0], [[300, 250], [336, 280]]). // Desktop & Tablet Landscape addSize([0, 0], []). // Phone build(); gptFluidMapping = googletag.sizeMapping(). addSize([0, 0], ['fluid']). build(); gptPrestitialMapping = googletag.sizeMapping(). addSize([600, 700], [[1, 1]]). // Desktop & Tablet Landscape addSize([0, 0], []). // Phone build(); gptInterscrollerMapping = googletag.sizeMapping(). addSize([1140, 445], []). addSize([1024, 768], [[1024, 768]]). addSize([768, 1024], [[768, 1024]]). addSize([480, 320], [[480, 320]]). addSize([320, 480], [[320, 480]]). build(); } //*********************************************** //End Define Size mapping based on client Viewport //*********************************************** //*********************************************** //Start detection for ad slots on page //*********************************************** var gptMasterPage = gpt_CheckForNULL($('#gptPage').val()); var gptMasterSite; if (gpt_AdFile === 'PU') { gptMasterSite = $('#gptSite').val(); } else { //JBS-CELL-LANCET gptMasterSite = "dev"; if (gpt_IsProd) { gptMasterSite = gpt_CheckForNULL($('#gptSite').val()); //If there is no master site, check for a defaultsite if (gptMasterSite == null) { gptMasterSite = gpt_CheckForNULL($('#gptDefaultSite').val()); } } else { //Dev ENV //If the page has no gptSite Value, assume no value which will disable ads if (gpt_CheckForNULL($('#gptSite').val()) === null) { gptMasterSite = null; } } //If there is no master Page, check for a Page using the URL if (gptMasterPage === null) { gptMasterPage = GPT_GetPageByURL(); } } $(".gpt-ad").each(function (index) { var gptPage = ''; var adSizeMapping = ''; var gptPOS; var gptTC; var gptNative; var adId; var gptSite; var tempSlot = null; if (gpt_IsProd) { //Check if the ad slot has it's own site defined if (typeof $(this).data('site') === 'undefined') { gptSite = gptMasterSite; } else { gptSite = gpt_CheckForNULL($(this).data('site')); } } else { gptSite = gptMasterSite; } if (gpt_AdFile === 'PU') { adId = $(this).attr('id'); } else { //JBS-CELL-LANCET adId = 'gpt-ad-' + index + 1; } if (gpt_CheckForNULL(gptSite) !== null) { gptSite_Debug = gptSite; gptPOS = parseInt($(this).data('pos')) || -1; if (gptPOS === -1) { gptPOS = index + 1; } //Check if the ad slot has it's own page defined gptPage = $(this).data('page'); if (gpt_CheckForNULL(gptPage) == null) { //Use the Master Page gptPage = gptMasterPage; } //If the page is not null, preceed it with a slash if (gptPage !== null) { gptPage = '/' + gptPage; } else { gptPage = ''; } gptPage_Debug = gptPage; gptTC = $(this).data('tc'); if (typeof gptTC === "undefined") { gptTC = ''; } gptNative = $(this).data('native'); if (typeof gptNative === "undefined") { gptNative = ''; } //Determine sizemapping based on data-adsize if (gpt_AdFile === 'PU') { switch ($(this).data('adsize')) { case 'tall': adSizeMapping = gptTallSizeMapping; tempSlot = googletag.defineSlot('/6053/els.' + gptSite + gptPage, [[120, 600], [160, 600], [300, 600]], adId); break; case 'rectangle': adSizeMapping = gptRectangleSizeMapping; tempSlot = googletag.defineSlot('/6053/els.' + gptSite + gptPage, [[300, 250]], adId); break; case 'rectangleshort': adSizeMapping = gptRectangleShortSizeMapping; tempSlot = googletag.defineSlot('/6053/els.' + gptSite + gptPage, [[300, 250], [320, 50], [300, 50]], adId); break; case 'wide': adSizeMapping = gptWideSizeMapping; tempSlot = googletag.defineSlot('/6053/els.' + gptSite + gptPage, [[728, 90], [320, 50], [300, 50]], adId); break; case 'widerectangle': adSizeMapping = gptWideRectangleSizeMapping; tempSlot = googletag.defineSlot('/6053/els.' + gptSite + gptPage, [[320, 50], [300, 50], [300, 250]], adId); break; case 'mobile': adSizeMapping = gptMobileSizeMapping; tempSlot = googletag.defineSlot('/6053/els.' + gptSite + gptPage, [[320, 50], [300, 50]], adId); break; case 'fluid': adSizeMapping = gptFluidMapping; tempSlot = googletag.defineSlot('/6053/els.' + gptSite + gptPage, 'fluid', adId); break; case 'prestitial': adSizeMapping = gptPrestitialMapping; tempSlot = googletag.defineSlot('/6053/els.' + gptSite + gptPage, [[1, 1]], adId); break; } } else { //JBS-CELL-LANCET switch ($(this).data('adsize')) { case 'cell-leaderboard': case 'leaderboard': adSizeMapping = gptLeaderboardSizeMapping; tempSlot = googletag.defineSlot('/6053/els.' + gptSite + gptPage, [[728, 90], [320, 50], [300, 50]], adId); break; case 'bottom': if (gpt_ResponsiveHomepage) { adSizeMapping = gptHomePageSidebarMapping; tempSlot = googletag.defineSlot('/6053/els.' + gptSite + gptPage, [[120, 600], [160, 600], [300, 600], [300, 250]], adId); } else { adSizeMapping = gptBoomBoxSizeMapping; tempSlot = googletag.defineSlot('/6053/els.' + gptSite + gptPage, [[300, 250]], adId); } break; case 'boombox': if (gpt_AdFile === "CELLJOURNAL" || gpt_AdFile == "CELLBUCKET") { if (gpt_ResponsiveHomepage) { adSizeMapping = gptCellHomePageSidebarMapping; tempSlot = googletag.defineSlot('/6053/els.' + gptSite + gptPage, [[120, 600], [160, 600], [300, 600], [300, 250], [336, 280]], adId); } else { adSizeMapping = gptBoomBoxSizeMapping; tempSlot = googletag.defineSlot('/6053/els.' + gptSite + gptPage, [[300, 250], [336, 280]], adId); } } else { adSizeMapping = gptBoomBoxSizeMapping; tempSlot = googletag.defineSlot('/6053/els.' + gptSite + gptPage, [[300, 250]], adId); } break; case 'interscroller': adSizeMapping = gptInterscrollerMapping; tempSlot = googletag.defineSlot('/6053/els.' + gptSite + gptPage, [[320, 480], [480, 320], [768, 1024], [1024, 768]], adId); break; case 'sidebar': case 'skyscraper': adSizeMapping = gptSideBarSizeMapping; tempSlot = googletag.defineSlot('/6053/els.' + gptSite + gptPage, [[120, 600], [160, 600], [300, 600], [300, 250]], adId); break; case 'native': case 'fluid': adSizeMapping = gptFluidMapping; tempSlot = googletag.defineSlot('/6053/els.' + gptSite + gptPage, 'fluid', adId); break; case 'prestitial': adSizeMapping = gptPrestitialMapping; tempSlot = googletag.defineSlot('/6053/els.' + gptSite + gptPage, 'fluid', adId); break; } } } //Ignore any invalid adsizes that could be on the page if (adSizeMapping !== '') { $(this).addClass('gpt-ad-defined'); if (gpt_AdFile !== 'PU') { $(this).attr('id', adId); } tempSlot.defineSizeMapping(adSizeMapping).addService(googletag.pubads()).setTargeting("pos", gptPOS); if (gptTC !== '') { tempSlot.setTargeting("tc", gptTC); } if (gptNative !== '') { tempSlot.setTargeting("native", gptNative); } gptEvent_Debug = gptEvent_Debug + $(this).data('adsize') + ' Requested<br>'; } else { gptInvalidAdSize_Debug = gptInvalidAdSize_Debug + "Invalid Size Found, Id: " + $(this).prop('id') + ', adSize: ' + $(this).data('adsize') + '<br>'; $(this).remove(); } }); if (gpt_CheckForNULL(gptInvalidAdSize_Debug) === null) { gptInvalidAdSize_Debug = "None Detected"; } //*********************************************** //End detection for ad slots on page //*********************************************** //*********************************************** //Start page level targeting //*********************************************** if (gpt_AdFile !== 'PU') { //Logged in or IP Access gpt_TargetAccessType(); //Check for Screenshot Client gpt_CheckSSC(); } //Check for DFP Test gpt_GetDFPTestId(); //Check for Additional Targeting gpt_GetAdditionalTargeting(); if (gpt_IsProd && gptContextualEnabled) { var gpt_ContextualRetry = false; //Check for Contextual Targeting if (gs_channels !== "DEFAULT") { var gpt_ContextualCategories = Array.from(gs_channels); for (var i = 0; i < gpt_ContextualCategories.length; i++) { if (gpt_ContextualCategories[i] == 'gx_retry') { gpt_ContextualRetry = true; } if (!gpt_ContextualCategories[i].startsWith("custom_")) { //Remove any tag that is not custom gpt_ContextualCategories.splice(i, 1); i--; } else { //Strip the 'custom_' from the tag gpt_ContextualCategories[i] = gpt_ContextualCategories[i].replace("custom_", "") } } if (gpt_ContextualCategories.length > 0) { googletag.pubads().setTargeting("gs_cat", gpt_ContextualCategories); } else { gpt_ContextualCategories = 'none'; } if (gpt_ContextualRetry) { gpt_ContextualCategories = "*Indexing*"; } gptContextualResult_Debug = gpt_ContextualCategories; } else { gptContextualResult_Debug = 'No segments found'; } } else { //Not Prod gptContextualResult_Debug = 'Not enabled'; var gpt_DevSite = gpt_CheckForNULL($('#gptSite').val(), "dev"); $('#gpt-Variables').append('<input type="hidden" id="gptEnvironment" value="' + gpt_DevSite + '">'); gpt_Target("Environment"); } //*********************************************** //End page level targeting //*********************************************** //Enable google dfp services if (parseInt($('#gptLazyLoading').val()) === 1) { googletag.pubads().enableLazyLoad({ fetchMarginPercent: 200, renderMarginPercent: 0, mobileScaling: 2.0 }); } else { googletag.pubads().enableSingleRequest(); } //Add Listener for RenderEnded googletag.pubads().addEventListener('slotRenderEnded', function (event) { if (!event.isEmpty) { if (typeof LocalAdLoaded === "function") { LocalAdLoaded(event); } if (gpt_ResponsiveHomepage) { if (typeof positionAd === "function") { positionAd(); } } if (event.size[0] == "480" || event.size[1] == "480") { $('.gpt-InScrollBox').css('display', 'block'); gptEvent_Debug = gptEvent_Debug + 'Interscroller ' + event.size + ' rendered: ' + gpt_GetElapsedTime() + '<br>'; } else { gptEvent_Debug = gptEvent_Debug + event.size + ' rendered: ' + gpt_GetElapsedTime() + '<br>'; } } }); if (gpt_AdFile !== 'PU') { googletag.pubads().collapseEmptyDivs(); } googletag.enableServices(); //Populate Defined Ad Slots $(".gpt-ad-defined").each(function (index) { var adId = $(this).attr('id'); googletag.cmd.push(function () { googletag.display(adId); }); }); gptStatus_Debug = 'GPT Complete'; }); } //-------------------------------------------------------------------------- function gpt_DisplayDebug() { //Clone the template and append to Body $(document.body).append($('#gpt-DebugDiv').clone()); $('#gpt-DebugDiv').remove(); //Populate the Values gpt_LoadDebugValues(); //Display and scroll to debug section $('.gpt-DebugDiv').css('display', 'block'); window.scrollTo(0, document.body.scrollHeight); } //-------------------------------------------------------------------------- function gpt_LoadDebugValues() { $('.gpt-DebugBtn').blur(); $('.gptVersion_Debug').text(gpt_Version); $('.gptAdFile_Debug').html(gpt_AdFile); $('.gptEvent_Debug').html(gptEvent_Debug); $('.gptCustomTargeting_Debug').html(gptCustomTargeting_Debug); $('.gptSite_Debug').text(gptSite_Debug); $('.gptContextualResult_Debug').text(gptContextualResult_Debug); $('.gptContextualInit_Debug').text(gptContextualInit_Debug); $('.gptContextualURL_Debug').text(gptContextualURL_Debug); $('.gptContextualReady_Debug').text(gptContextualReady_Debug); $('.gptMoatReady_Debug').text(gptMoatReady_Debug); $('.gptMoatInit_Debug').text(gptMoatInit_Debug); $('.gptTestENV_Debug').text(gptTestENV_Debug); $('.gptDisableAds_Debug').text(gptDisableAds_Debug); $('.gptStatus_Debug').text(gptStatus_Debug); $('.gptPage_Debug').text(gptPage_Debug); $('.gptInvalidAdSize_Debug').html(gptInvalidAdSize_Debug); } //-------------------------------------------------------------------------- function gpt_GrapeShotDebug() { $('.gpt-DebugBtn').blur(); window.open("http://admin-elsevier.grapeshot.co.uk/custom/bookmarklet.cgi?blocking=1&vn=2&url=" + encodeURIComponent(document.location), "GRAPESHOT_POPUP", "width=650,height=600,scrollbars=yes,screenX=40,screenY=50,menubar=no,toolbar=no,resizable=yes", "Custom").focus(); } //-------------------------------------------------------------------------- function gpt_ShowConsole() { $('.gpt-DebugBtn').blur(); googletag.openConsole(); } //-------------------------------------------------------------------------- </script> </div> </div> <div data-widget-id="53023812-5eb3-476f-8922-6f6f95be0a5c" data-widget-name="ux3-layout-widget"><header class="header base fixed"> <div class="widget literatumAd none adplaceholder adplaceholder--header js__adToHide widget-horizontalAd" id="ad532c9c-4e0f-4b0d-8b27-9bd0ddbdb190"> <div class="wrapped " > <div class="widget-body body body-horizontalAd "><div class="horizontalAdContainer"> <div class="horizontalAdLabelContainer"> <div class="horizontalAdLabel"> <img src="/templates/jsp/_style2/_marlin/images/bg_adHoriz.gif" alt="Advertisement"/> </div> </div> <div class="horizontalAd"> <div class="pb-ad"> <div class="gpt-ad" data-adsize="leaderboard"></div> </div> </div> </div></div> </div> </div> <div data-widget-def="ux3-layout-widget" data-widget-id="3bd430f7-bd17-4546-89a2-5b0ca3b18cdf" class="header__wrapper clearfix" data-db-parent-of="quickSearch"> <div data-widget-id="3bd430f7-bd17-4546-89a2-5b0ca3b18cdf" data-widget-name="ux3-layout-widget"><div class="col-xs-6 col-lg-6 journal-logos-wrapper header__left-side"> <div class="journal-logos"> <span data-widget-id="ecdbcba0-b4aa-4389-a4c7-33705333b11e" data-widget-name="ux3-general-image"><a href="/home" title="Cytotherapy"><img alt="Cytotherapy" src="/pb-assets/ux3/logos/ha/jcyt_200504-1588616413253.svg"/></a></span> </div> <div class="journal-logos"> <span data-widget-id="461d3ef5-f2da-4b8b-99b6-8a86500c809f" data-widget-name="ux3-general-image"><a href="https://isctglobal.org/" title="ISCT"><img alt="ISCT" src="/pb-assets/ux3/logos/ha/jcyt_ISCT-1587664230747.png"/></a></span> </div> </div><div class="col-xs-6 col-lg-6"> <div data-widget-id="27014d70-9f94-467d-857b-805d256132d2" data-widget-name="ux3-layout-widget"><div class="header__nav row"> <ul data-widget-id="337ee8a8-34c0-420d-84ae-7906e01fd189" data-widget-name="UX3ProfileLinksWidget" class="rlist rlist--inline profile-links"><li class="profile-links__loginHtml"><a href="https://www.editorialmanager.com/jcyt/default1.aspx" target="_blank">Submit </a></li><li class="profile-links__logIn"><a href="/action/showLogin?redirectUri=https%3A%2F%2Fwww.isct-cytotherapy.org%2Farticle%2FS1465-3249%2823%2900064-6%2Ffulltext&pii=S1465-3249%2823%2900064-6" title="Log in" class="show-login">Log in</a></li><li class="profile-links__register"><a href="/action/registration?redirectUri=https%3A%2F%2Fwww.isct-cytotherapy.org%2Farticle%2FS1465-3249%2823%2900064-6%2Ffulltext&directReg=true" title="Register a username and password for free">Register</a></li><li class="hidden-lg"><div class="dropBlock profile-links__user-list__wrapper"><a href="#" data-db-target-for="loginMenu" aria-expanded="false" aria-controls="login-links" title="LogIn" class="profile-links__logIn__mobile">Log in</a><div data-db-target-of="loginMenu" id="login-links" class="dropBlock__holder profile-links__user-list__holder"><ul class="rlist article-tools__sub-list"><li><a href="https://www.editorialmanager.com/jcyt/default1.aspx" target="_blank">Submit </a></li><li><a href="/action/showLogin?redirectUri=https%3A%2F%2Fwww.isct-cytotherapy.org%2Farticle%2FS1465-3249%2823%2900064-6%2Ffulltext&pii=S1465-3249%2823%2900064-6" title="Log in" class="show-login">Log in</a></li></ul></div></div></li><li class="profile-links__subscribe"><a href="/action/ecommerce" title="Subscribe">Subscribe</a></li><li class="profile-links__claim"><a href="/action/activateClaim" title="Claim your online subscription">Claim</a></li></ul> </div></div> </div></div> </div> <div class="widget csasInstitutionBanner none widget-none" id="ee8e0108-277d-418e-a042-5980d028efd5"> <div class="wrapped " > <div class="widget-body body body-none "><div class="ui-state-highlight ui-corner-all csas-institution-banner hidden" data-doi="10.1016/j.jcyt.2023.03.002"> <span class="ui-icon ui-icon-close banner-close"></span> <p> Access provided by <span class="accountName"></span> </p> </div> <style> .csas-institution-banner { padding: 10px 0 0 10px; margin: 5px; } .csas-institution-banner.ui-state-highlight .ui-icon { background-image: url("/templates/jsp/css/jquery-ui-1.10.2/base/images/ui-icons_454545_256x240.png"); margin-right: 5px; margin-top: -4px; } .csas-institution-banner .banner-close { float: right; } </style> <script> function resetBanner(doi) { $.get('/action/getAccount?doi=' + doi, function(data) { if (data) { $(".csas-institution-banner p .accountName").html(data); $(".csasInstitutionBanner").fadeIn(); $(".csas-institution-banner").fadeIn(); } }); } var flag = 0; $(document).ready(function() { if(!$(".csas-institution-banner").is(":visible")){ $(".csasInstitutionBanner").hide(); } $(".banner-close").click(function() { $.get("/action/dismissBanner", function(data) { $(".csasInstitutionBanner").fadeOut(function () { if(typeof UX !== 'undefined') { UX.pageBody.init(); } }); }); }); $(".articleContent .tabs li[role='tab'].showFullText").click(function() { flag = 1; }); $(document).on("reloadTabsContent", function() { var isSelected = $(".articleContent .tabs li[role='tab'].showFullText").hasClass("active"); if (isSelected) { var isHidden = $(".csas-institution-banner").is(".hidden"); if (!isHidden) { resetBanner($(".csas-institution-banner").data("doi")); console.log("fadeIn"); } } else { $(".csas-institution-banner").fadeOut(); console.log("fadeOut"); } flag = 0; }); $(document).on("click", ".articleContent .tabs li[role='tab']", function() { }); }); </script></div> </div> </div> </header></div> <div data-widget-def="graphQueryWidget" data-widget-id="fad9a144-1a93-40be-baba-cf44f74c2b48" class="ux3"> <div class="widget graphQueryWidget none top-padding-handler noMargin axel-mega-menu widget-none widget-compact-all" id="fad9a144-1a93-40be-baba-cf44f74c2b48"> <div class="wrapped " > <div class="widget-body body body-none body-compact-all"><nav id="mega-menu-nav" role="navigation" class="mega-menu-nav">  <div class="mega-menu-nav__wrapper"> <button class="mega-menu__toggle"><span class="sr-only">Main menu</span><i aria-hidden="true" class="icon-gizmo-hamburger"></i></button> <ul role="menubar" class="mega-menu rlist"> <li role="presentation" class="mega-menu__item"><a id="main-menu-link-1" aria-haspopup="true" href="javascript:void(0)" role="menuitem" aria-controls="main-menu-panel-1" data-item-link="main-menu-link-1" data-index="0" class="mega-menu__item-link menu-link"><span>Articles</span></a> <div id="main-menu-panel-1" aria-labelledby="main-menu-link-1" data-item-wrapper="main-menu-link-1" aria-expanded="false" class="mega-menu__item-wrapper"> <ul class="sub-menu rlist mega-menu__sub-menu-heading"> <li style="grid-column: 1/2" class="double-width sub-menu__item"> <div aria-label="Menu dropzone section" tabindex="-1" class="listDropZone"> <div class="hidden-xs hidden-sm"> <div class="cover-image"><div class="cover-image__thumb"><a href="/issue/S1465-3249(24)X0013-4"><img src="/cms/asset/atypon:cms:attachment:img:d251e6:rev:1731462886933-15435:pii:S1465324924X00134/cover.tif.jpg" alt="Cover Image - Cytotherapy, Volume 26, Issue 12"/></a></div><div class="cover-image__meta"></div></div> </div> </div> </li> <li style="grid-column: 2/3" class="double-width sub-menu__item"> <h4 data-item-link="main-menu-link-1-2" class="sub-menu__heading">Latest </h4> <ul role="menubar" data-index="0" class="rlist heading-list col-count-1"> <li role="presentation" class="menu-link__wrapper"><a href="/inpress" data-index="0" role="menuitem" class="sub-menu__item-link menu-link"><span>Articles in Press</span></a></li> <li role="presentation" class="menu-link__wrapper"><a href="/current" data-index="1" role="menuitem" class="sub-menu__item-link menu-link"><span>Current issue</span></a></li> <li role="presentation" class="menu-link__wrapper"><a href="/issues" data-index="2" role="menuitem" class="sub-menu__item-link menu-link"><span>Past Issues</span></a></li> </ul> </li> <li style="grid-column: 3/5" class="double-width sub-menu__item"> <div aria-label="Menu dropzone section" tabindex="-1" class="listDropZone"> <div data-widget-def="UX3MultiSearchWidget" data-widget-id="c50cd7b9-13da-44c4-88f1-d8b1dd5b2ece" class="hidden-xs hidden-sm"> <h2>Popular Articles</h2> <div class="navarticlecss"> <ul class="publication-list rlist publication-list--list"><li class="search__item clearfix separator"><div class="search__item__body"><div class="meta__header"><div class="meta__type-access"><div class="meta__type">FULL-LENGTH ARTICLE Stem Cell Therapy</div></div></div><span class="hlFld-Title"><h4 class="meta__title"><a href="/article/S1465-3249(24)00730-8/fulltext" class="full-title-multi-search">Considerations for the development of iPSC-derived cell therapies: a review of key challenges by the JSRM-ISCT iPSC Committee</a></h4></span><ul class="meta__authors rlist--inline comma" title="list of authors"><li>Madrid et al.</li></ul><div class="action-links"></div><div class="alt-multi-search__article__preview"></div></div></li><li class="search__item clearfix separator"><div class="search__item__body"><div class="meta__header"><div class="meta__type-access"><div class="meta__type">Review Article</div></div></div><span class="hlFld-Title"><h4 class="meta__title"><a href="/article/S1465-3249(22)01075-1/fulltext" class="full-title-multi-search">The NK-92 cell line—30 years later: its impact on natural killer cell research and treatment of cancer</a></h4></span><ul class="meta__authors rlist--inline comma" title="list of authors"><li>Hans Klingemann</li></ul><div class="action-links"></div><div class="alt-multi-search__article__preview"></div></div></li><li class="search__item clearfix separator"><div class="search__item__body"><div class="meta__header"><div class="meta__type-access"><div class="meta__type">Full-Length Article</div></div></div><span class="hlFld-Title"><h4 class="meta__title"><a href="/article/S1465-3249(24)00927-7/fulltext" class="full-title-multi-search">Rapid manufacture of low-seed CAR-T cells in a GMP-grade hollow-fiber bioreactor platform</a></h4></span><ul class="meta__authors rlist--inline comma" title="list of authors"><li>Marshall et al.</li></ul><div class="action-links"></div><div class="alt-multi-search__article__preview"></div></div></li></ul> </div> </div> </div> </li> <li style="grid-column: 5/7" class="double-width sub-menu__item"> <div aria-label="Menu dropzone section" tabindex="-1" class="listDropZone"> <h2>Latest Articles</h2> <div class="navarticlecss"> <ul class="publication-list rlist publication-list--list"><li class="search__item clearfix separator"><div class="search__item__body"><div class="meta__header"><div class="meta__type-access"><div class="meta__type">Full-length article</div></div></div><span class="hlFld-Title"><h4 class="meta__title"><a href="/article/S1465-3249(24)00928-9/fulltext" class="full-title-multi-search">Efficacy of Chimeric Antigen Receptor Engineered Natural Killer Cells in the Treatment of Hematologic Malignancies: A Systematic Review and Meta-Analysis of Preclinical Studies</a></h4></span><ul class="meta__authors rlist--inline comma" title="list of authors"><li>Bastin et al.</li></ul><div class="action-links"></div><div class="alt-multi-search__article__preview"></div></div></li><li class="search__item clearfix separator"><div class="search__item__body"><div class="meta__header"><div class="meta__type-access"><div class="meta__type">Corrigendum</div></div></div><span class="hlFld-Title"><h4 class="meta__title"><a href="/article/S1465-3249(24)00936-8/fulltext" class="full-title-multi-search">Corrigendum to Real-time semantic segmentation and anomaly detection of functional images for cell therapy manufacturing Cytotherapy 25 (2023) 1361 - 1369</a></h4></span><ul class="meta__authors rlist--inline comma" title="list of authors"><li>Chen et al.</li></ul><div class="action-links"></div><div class="alt-multi-search__article__preview"></div></div></li><li class="search__item clearfix separator"><div class="search__item__body"><div class="meta__header"><div class="meta__type-access"><div class="meta__type">Review article</div></div></div><span class="hlFld-Title"><h4 class="meta__title"><a href="/article/S1465-3249(24)00940-X/fulltext" class="full-title-multi-search">Role of Mesenchymal Stromal Cell Secretome on Recovery from Cellular Senescence: An Overview</a></h4></span><ul class="meta__authors rlist--inline comma" title="list of authors"><li>de Nazaré Lins de Brito et al.</li></ul><div class="action-links"></div><div class="alt-multi-search__article__preview"></div></div></li></ul> </div> </div> </li> </ul> </div> </li> <li role="presentation" class="mega-menu__item"><a id="main-menu-link-2" aria-haspopup="true" href="javascript:void(0)" role="menuitem" aria-controls="main-menu-panel-2" data-item-link="main-menu-link-2" data-index="1" class="mega-menu__item-link menu-link"><span>Publish</span></a> <div id="main-menu-panel-2" aria-labelledby="main-menu-link-2" data-item-wrapper="main-menu-link-2" aria-expanded="false" class="mega-menu__item-wrapper"> <ul class="sub-menu rlist mega-menu__sub-menu-heading"> <li style="grid-column: 1/2" class="double-width sub-menu__item"> <h4 data-item-link="main-menu-link-2-1" class="sub-menu__heading">For Authors </h4> <ul role="menubar" data-index="0" class="rlist heading-list col-count-1"> <li role="presentation" class="menu-link__wrapper"><a href="https://www.editorialmanager.com/jcyt/default2.aspx" data-index="0" target="_blank" role="menuitem" class="sub-menu__item-link menu-link"><span>Submit Article <div class="external-icon"></div><span class="sr-only">External Link</span></span></a></li> <li role="presentation" class="menu-link__wrapper"><a href="/authorinfo" data-index="1" role="menuitem" class="sub-menu__item-link menu-link"><span>Guide for Authors</span></a></li> <li role="presentation" class="menu-link__wrapper"><a href="/aims" data-index="2" role="menuitem" class="sub-menu__item-link menu-link"><span>Aims & Scope</span></a></li> <li role="presentation" class="menu-link__wrapper"><a href="https://www.elsevier.com/journals/cytotherapy/1465-3249/open-access-options" data-index="3" target="_blank" role="menuitem" class="sub-menu__item-link menu-link"><span>Open Access Information <div class="external-icon"></div><span class="sr-only">External Link</span></span></a></li> <li role="presentation" class="menu-link__wrapper"><a href="https://researcheracademy.elsevier.com/" data-index="4" target="_blank" role="menuitem" class="sub-menu__item-link menu-link"><span>Researcher Academy <div class="external-icon"></div><span class="sr-only">External Link</span></span></a></li> </ul> </li> </ul> </div> </li> <li role="presentation" class="mega-menu__item"><a id="main-menu-link-3" aria-haspopup="true" href="javascript:void(0)" role="menuitem" aria-controls="main-menu-panel-3" data-item-link="main-menu-link-3" data-index="2" class="mega-menu__item-link menu-link"><span>Topics</span></a> <div id="main-menu-panel-3" aria-labelledby="main-menu-link-3" data-item-wrapper="main-menu-link-3" aria-expanded="false" class="mega-menu__item-wrapper"> <ul class="sub-menu rlist mega-menu__sub-menu-heading"> <li style="grid-column: 1/2" class="double-width sub-menu__item"> <h4 data-item-link="main-menu-link-3-1" class="sub-menu__heading">Collections </h4> <ul role="menubar" data-index="0" class="rlist heading-list col-count-1"> <li role="presentation" class="menu-link__wrapper"><a href="/content/exosomes_mini-series" data-index="0" role="menuitem" class="sub-menu__item-link menu-link"><span>Exosomes Mini-Series</span></a></li> <li role="presentation" class="menu-link__wrapper"><a href="/content/jcyt-covid-19" data-index="1" role="menuitem" class="sub-menu__item-link menu-link"><span>COVID-19 Article Collection</span></a></li> <li role="presentation" class="menu-link__wrapper"><a href="/content/jcyt-immunotherapy-articles" data-index="2" role="menuitem" class="sub-menu__item-link menu-link"><span>Immunotherapy Articles</span></a></li> <li role="presentation" class="menu-link__wrapper"><a href="/content/jcyt-isct-publications" data-index="3" role="menuitem" class="sub-menu__item-link menu-link"><span>ISCT Publications</span></a></li> <li role="presentation" class="menu-link__wrapper"><a href="/content/jcyt-manufacturing-processes-articles" data-index="4" role="menuitem" class="sub-menu__item-link menu-link"><span>Manufacturing Processes Articles</span></a></li> <li role="presentation" class="menu-link__wrapper"><a href="/content/jcyt-stem-cell-therapy-articles" data-index="5" role="menuitem" class="sub-menu__item-link menu-link"><span>Stem Cell Therapy Articles</span></a></li> <li role="presentation" class="menu-link__wrapper"><a href="/content/jcyt-stromal-cell-therapy" data-index="6" role="menuitem" class="sub-menu__item-link menu-link"><span>Stromal Cell Therapy Articles</span></a></li> <li role="presentation" class="menu-link__wrapper"><a href="/content/jcyt-talking-with-giants" data-index="7" role="menuitem" class="sub-menu__item-link menu-link"><span>Talking with Giants</span></a></li> </ul> </li> <li style="grid-column: 2/4" class="double-width sub-menu__item"> <h4 data-item-link="main-menu-link-3-2" class="sub-menu__heading">Special Issues </h4> <ul role="menubar" data-index="1" class="rlist heading-list col-count-2"> <li role="presentation" class="menu-link__wrapper"><a href="/issue/S1465-3249(19)X0003-1" data-index="0" role="menuitem" class="sub-menu__item-link menu-link"><span>Evaluation of Manufactured Cellular Products</span></a></li> <li role="presentation" class="menu-link__wrapper"><a href="/issue/S1465-3249(18)X0003-6" data-index="1" role="menuitem" class="sub-menu__item-link menu-link"><span>ISCT 2018 Annual Meeting</span></a></li> <li role="presentation" class="menu-link__wrapper"><a href="/issue/S1465-3249(13)X0014-3" data-index="2" role="menuitem" class="sub-menu__item-link menu-link"><span>19th ISCT Annual Meeting</span></a></li> <li role="presentation" class="menu-link__wrapper"><a href="/issue/S1465-3249(14)X0004-6" data-index="3" role="menuitem" class="sub-menu__item-link menu-link"><span>20th Annual ISCT Meeting</span></a></li> <li role="presentation" class="menu-link__wrapper"><a href="/content/jcyt-special-issue-umbilical-cord-blood" data-index="4" role="menuitem" class="sub-menu__item-link menu-link"><span>Umbilical Cord Blood: Advances and Opportunities</span></a></li> <li role="presentation" class="menu-link__wrapper"><a href="/issue/S1465-3249(15)X0002-8" data-index="5" role="menuitem" class="sub-menu__item-link menu-link"><span>21st ISCT Annual Meeting</span></a></li> <li role="presentation" class="menu-link__wrapper"><a href="/issue/S1465-3249(17)X0011-X" data-index="6" role="menuitem" class="sub-menu__item-link menu-link"><span>Cell Therapy for Infectious Diseases</span></a></li> <li role="presentation" class="menu-link__wrapper"><a href="/issue/S1465-3249(17)X0004-2" data-index="7" role="menuitem" class="sub-menu__item-link menu-link"><span>ISCT 2017 Annual Meeting</span></a></li> <li role="presentation" class="menu-link__wrapper"><a href="/issue/S1465-3249(16)X0005-9" data-index="8" role="menuitem" class="sub-menu__item-link menu-link"><span>22nd Annual ISCT Meeting</span></a></li> <li role="presentation" class="menu-link__wrapper"><a href="/issue/S1465-3249(16)X0011-4" data-index="9" role="menuitem" class="sub-menu__item-link menu-link"><span>SI: Gene Modified Cell Therapies</span></a></li> </ul> </li> </ul> </div> </li> <li role="presentation" class="mega-menu__item"><a id="main-menu-link-4" aria-haspopup="true" href="javascript:void(0)" role="menuitem" aria-controls="main-menu-panel-4" data-item-link="main-menu-link-4" data-index="3" class="mega-menu__item-link menu-link"><span>About</span></a> <div id="main-menu-panel-4" aria-labelledby="main-menu-link-4" data-item-wrapper="main-menu-link-4" aria-expanded="false" class="mega-menu__item-wrapper"> <ul class="sub-menu rlist mega-menu__sub-menu-heading"> <li style="grid-column: 1/2" class="double-width sub-menu__item"> <h4 data-item-link="main-menu-link-4-1" class="sub-menu__heading">Society </h4> <ul role="menubar" data-index="0" class="rlist heading-list col-count-1"> <li role="presentation" class="menu-link__wrapper"><a href="http://www.celltherapysociety.org" data-index="0" target="_blank" role="menuitem" class="sub-menu__item-link menu-link"><span>ISCT <div class="external-icon"></div><span class="sr-only">External Link</span></span></a></li> <li role="presentation" class="menu-link__wrapper"><a href="/edboard" data-index="1" role="menuitem" class="sub-menu__item-link menu-link"><span>Editorial Board</span></a></li> </ul> </li> <li style="grid-column: 2/3" class="double-width sub-menu__item"> <h4 data-item-link="main-menu-link-4-2" class="sub-menu__heading">Journal Information </h4> <ul role="menubar" data-index="1" class="rlist heading-list col-count-1"> <li role="presentation" class="menu-link__wrapper"><a href="/aims" data-index="0" role="menuitem" class="sub-menu__item-link menu-link"><span>Aims & Scope</span></a></li> <li role="presentation" class="menu-link__wrapper"><a href="/content/permission" data-index="1" role="menuitem" class="sub-menu__item-link menu-link"><span>Permissions</span></a></li> <li role="presentation" class="menu-link__wrapper"><a href="https://www.medreprints.com" data-index="2" target="_blank" role="menuitem" class="sub-menu__item-link menu-link"><span>Reprints <div class="external-icon"></div><span class="sr-only">External Link</span></span></a></li> <li role="presentation" class="menu-link__wrapper"><a href="/abstracting" data-index="3" role="menuitem" class="sub-menu__item-link menu-link"><span>Abstracting & Indexing</span></a></li> </ul> </li> <li style="grid-column: 3/4" class="double-width sub-menu__item"> <h4 data-item-link="main-menu-link-4-3" class="sub-menu__heading">Access </h4> <ul role="menubar" data-index="2" class="rlist heading-list col-count-1"> <li role="presentation" class="menu-link__wrapper"><a href="/action/ecommerce" data-index="0" role="menuitem" class="sub-menu__item-link menu-link"><span>Subscribe</span></a></li> <li role="presentation" class="menu-link__wrapper"><a href="/claim/activate" data-index="1" role="menuitem" class="sub-menu__item-link menu-link"><span>Activate Online Access</span></a></li> </ul> </li> </ul> </div> </li> <li role="presentation" class="mega-menu__item"><a id="main-menu-link-5" aria-haspopup="true" href="javascript:void(0)" role="menuitem" aria-controls="main-menu-panel-5" data-item-link="main-menu-link-5" data-index="4" class="mega-menu__item-link menu-link"><span>Contact</span></a> <div id="main-menu-panel-5" aria-labelledby="main-menu-link-5" data-item-wrapper="main-menu-link-5" aria-expanded="false" class="mega-menu__item-wrapper"> <ul class="sub-menu rlist mega-menu__sub-menu-heading"> <li style="grid-column: 1/2" class="double-width sub-menu__item"> <h4 data-item-link="main-menu-link-5-1" class="sub-menu__heading">Contact </h4> <ul role="menubar" data-index="0" class="rlist heading-list col-count-1"> <li role="presentation" class="menu-link__wrapper"><a href="/contact-us" data-index="0" role="menuitem" class="sub-menu__item-link menu-link"><span>Contact Us</span></a></li> <li role="presentation" class="menu-link__wrapper"><a href="http://www.myhealthtalent.com/" data-index="1" target="_blank" role="menuitem" class="sub-menu__item-link menu-link"><span>Career Opportunities <div class="external-icon"></div><span class="sr-only">External Link</span></span></a></li> <li role="presentation" class="menu-link__wrapper"><a href="http://www.elsmediakits.com" data-index="2" target="_blank" role="menuitem" class="sub-menu__item-link menu-link"><span>Advertise with Us <div class="external-icon"></div><span class="sr-only">External Link</span></span></a></li> <li role="presentation" class="menu-link__wrapper"><a href="http://www.elsevierhealth.com/index.jsp" data-index="3" target="_blank" role="menuitem" class="sub-menu__item-link menu-link"><span>Go to Product Catalog <div class="external-icon"></div><span class="sr-only">External Link</span></span></a></li> </ul> </li> <li style="grid-column: 2/3" class="double-width sub-menu__item"> <h4 data-item-link="main-menu-link-5-2" class="sub-menu__heading">Follow Us </h4> <ul role="menubar" data-index="1" class="rlist heading-list col-count-1"> <li role="presentation" class="menu-link__wrapper"><a href="/action/doUpdateAlertSettings?action=addJournal&journalCode=JCYT&referrer=/" data-index="0" role="menuitem" class="sub-menu__item-link menu-link"><span>New Content Alerts</span></a></li> <li role="presentation" class="menu-link__wrapper"><a href="https://twitter.com/cytotherapy?ref_src=twsrc%5Etfw%7Ctwcamp%5Eembeddedtimeline%7Ctwterm%5Escreen-name%3Acytotherapy%7Ctwcon%5Es2" data-index="1" target="_blank" role="menuitem" class="sub-menu__item-link menu-link"><span>Twitter <div class="external-icon"></div><span class="sr-only">External Link</span></span></a></li> </ul> </li> </ul> </div> </li> </ul> <div class="mega-menu-nav__quick-search"> <div data-widget-id="4b13527a-8285-4636-ac31-0e0ddddf175f" data-widget-name="UX3QuickSearchWidget" class="quick-search"><div class="dropBlock"><form action="https://www.isct-cytotherapy.org/action/doSearch?journalCode=jcyt" name="quickSearchBar" method="get" title="Quick Search"><input id="type" type="hidden" value="quicksearch" name="type"/><div class="quick-search__toggle"><input id="searchText" type="text" name="text1" placeholder="Search for..." enterkeyhint="search" autocomplete="off" data-contributors-conf="3" data-topics-conf="3" data-publication-titles-conf="3" data-history-items-conf="3" data-group-titles-conf="3" data-publication-items-conf="3" aria-label="Enter a search term" class="searchText searchText-autocomplete"/><button type="submit" title="Search" aria-label="Submit the search form" class="btn quick-search__button icon-search"><span>Go search</span></button><a href="https://www.isct-cytotherapy.org/search/advanced?SeriesKey=jcyt&ISSN=1465-3249&journalCode=jcyt" title="Advanced search" class="quick-search__advanced-link">Advanced search</a></div><div class="quick-search__box"><div class="quick-search__box-inner"><div class="quick-search__box-wrapper"><select name="field1" aria-label="Select a search area"><option value="AllField">All content</option><option value="Title">Article title</option><option value="Contrib">Authors</option><option value="Keyword">Keywords</option><option value="Abstract">Abstract</option><option value="AbstractTitleKeywordFilterField">Article title, abstract, keywords</option></select><a href="https://www.isct-cytotherapy.org/search/advanced?SeriesKey=jcyt&ISSN=1465-3249&journalCode=jcyt" title="Advanced search" class="quick-search__advanced-link">Advanced search</a></div><a href="javascript:void(0)" aria-label="Close search options" title="Close search options" class="quick-search__box-close"><i aria-hidden="true" class="icon-tools_close"></i></a></div></div><div class="quick-search__alert hidden"><p>Please enter a term before submitting your search.</p><a href="#" class="quick-search__alert--close"> Ok</a></div></form></div></div> </div> </div> </nav> <div id="page-body-id" class="page-body-flag"></div></div> </div> </div> </div> <div data-widget-id="cce513c3-ede2-454b-83a2-b235c17a37ed" data-widget-name="UX3HTMLWidget"></div> <div class="widget axelPublicationContent none widget-none" id="922bea2a-77ad-4d06-a464-4510160d2279"> <div class="wrapped " > <div class="widget-body body body-none "><link id="build-style-article" rel="stylesheet" type="text/css" href="/products/marlin/ha/releasedAssets/css/build-article-45520a2122a8fee68553.css"/><article xmlns="http://www.w3.org/1999/xhtml" data-design="pill" data-has="right-rail long-title" vocab="http://schema.org/" typeof="ScholarlyArticle" data-pii="S1465-3249(23)00064-6" lang="en" dir="ltr"><div data-core-wrapper="header"><header data-extent="frontmatter"><div class="core-container"><div data-article-access="full" data-article-access-type="open" class="meta-panel"><span class="meta-panel__left"><span class="meta-panel__type"><span>ISCT Committee Paper</span></span></span><span class="meta-panel__middle"><span class="meta-panel__volumeIssue"><a href="/issue/S1465-3249(22)X0022-4"><span>Volume 25</span>, <span>Issue 9</span></a></span><span class="meta-panel__pages"><span>p920-929</span></span><span class="meta-panel__onlineDate">September 2023</span></span><span class="meta-panel__right"><span class="meta-panel__access meta-panel__access--open"><span>Open access</span></span></span></div><h1 property="name">International Society for Cell & Gene Therapy Position Paper: Key considerations to support evidence-based cell and gene therapies and oppose marketing of unproven products</h1><div class="contributors"><span class="authors"><span role="list"><span property="author" typeof="Person" role="listitem" class="corresponding-author"><a href="#au0001"><span property="givenName">Laertis</span> <span property="familyName">Ikonomou</span></a><sup class="xref"><a href="#aff0001" property="affiliation" typeof="Organization" role="doc-noteref">1</a>,<a href="#aff0002" property="affiliation" typeof="Organization" role="doc-noteref">2</a></sup> <a id="ead0001" href="mailto:laertisi@buffalo.edu" property="email" title="Send email to Laertis Ikonomou">laertisi@buffalo.edu</a></span> ∙ <span property="author" typeof="Person" role="listitem"><a href="#au0002"><span property="givenName">Natividad</span> <span property="familyName">Cuende</span></a><sup class="xref"><a href="#aff0003" property="affiliation" typeof="Organization" role="doc-noteref">3</a>,<a href="#fn1" role="doc-noteref">⁎⁎</a></sup></span> ∙ <span property="author" typeof="Person" role="listitem"><a href="#au0003"><span property="givenName">Miguel</span> <span property="familyName">Forte</span></a><sup class="xref"><a href="#aff0004" property="affiliation" typeof="Organization" role="doc-noteref">4</a>,<a href="#fn1" role="doc-noteref">⁎⁎</a></sup></span><span data-displayed-on="all"> ∙ … </span><span data-hidden-on="all"> ∙ <span property="author" typeof="Person" role="listitem"><a href="#au0004"><span property="givenName">Bambi J.</span> <span property="familyName">Grilley</span></a><sup class="xref"><a href="#aff0005" property="affiliation" typeof="Organization" role="doc-noteref">5</a>,<a href="#aff0006" property="affiliation" typeof="Organization" role="doc-noteref">6</a>,<a href="#fn1" role="doc-noteref">⁎⁎</a></sup></span></span><span data-hidden-on="all"> ∙ <span property="author" typeof="Person" role="listitem"><a href="#au0005"><span property="givenName">Aaron D.</span> <span property="familyName">Levine</span></a><sup class="xref"><a href="#aff0007" property="affiliation" typeof="Organization" role="doc-noteref">7</a>,<a href="#fn1" role="doc-noteref">⁎⁎</a></sup></span></span><span data-hidden-on="all"> ∙ <span property="author" typeof="Person" role="listitem"><a href="#au0006"><span property="givenName">Megan</span> <span property="familyName">Munsie</span></a><sup class="xref"><a href="#aff0008" property="affiliation" typeof="Organization" role="doc-noteref">8</a>,<a href="#aff0009" property="affiliation" typeof="Organization" role="doc-noteref">9</a>,<a href="#fn1" role="doc-noteref">⁎⁎</a></sup></span></span><span data-hidden-on="all"> ∙ <span property="author" typeof="Person" role="listitem"><a href="#au0007"><span property="givenName">John E.J.</span> <span property="familyName">Rasko</span></a><sup class="xref"><a href="#aff0010" property="affiliation" typeof="Organization" role="doc-noteref">10</a>,<a href="#aff0011" property="affiliation" typeof="Organization" role="doc-noteref">11</a>,<a href="#aff0012" property="affiliation" typeof="Organization" role="doc-noteref">12</a>,<a href="#fn1" role="doc-noteref">⁎⁎</a></sup></span></span><span data-hidden-on="all"> ∙ <span property="author" typeof="Person" role="listitem"><a href="#au0008"><span property="givenName">Leigh</span> <span property="familyName">Turner</span></a><sup class="xref"><a href="#aff0013" property="affiliation" typeof="Organization" role="doc-noteref">13</a>,<a href="#fn1" role="doc-noteref">⁎⁎</a></sup></span></span><span data-hidden-on="all"> ∙ <span property="author" typeof="Person" role="listitem"><a href="#au0009"><span property="givenName">Hamid R.</span> <span property="familyName">Bidkhori</span></a><sup class="xref"><a href="#aff0014" property="affiliation" typeof="Organization" role="doc-noteref">14</a></sup></span></span><span data-hidden-on="all"> ∙ <span property="author" typeof="Person" role="listitem"><a href="#au0010"><span property="givenName">Rachele</span> <span property="familyName">Ciccocioppo</span></a><sup class="xref"><a href="#aff0015" property="affiliation" typeof="Organization" role="doc-noteref">15</a></sup></span></span><span data-hidden-on="all"> ∙ <span property="author" typeof="Person" role="listitem"><a href="#au0011"><span property="givenName">Felix</span> <span property="familyName">Grignon</span></a><sup class="xref"><a href="#aff0016" property="affiliation" typeof="Organization" role="doc-noteref">16</a></sup></span></span><span data-hidden-on="all"> ∙ <span property="author" typeof="Person" role="listitem"><a href="#au0012"><span property="givenName">Alok</span> <span property="familyName">Srivastava</span></a><sup class="xref"><a href="#aff0017" property="affiliation" typeof="Organization" role="doc-noteref">17</a></sup></span></span><span data-hidden-on="all"> ∙ <span property="author" typeof="Person" role="listitem"><a href="#au0013"><span property="givenName">Daniel J.</span> <span property="familyName">Weiss</span></a><sup class="xref"><a href="#aff0018" property="affiliation" typeof="Organization" role="doc-noteref">18</a></sup></span></span> ∙ <span property="author" typeof="Person" role="listitem"><a href="#au0014"><span property="givenName">Patricia</span> <span property="familyName">Zettler</span></a><sup class="xref"><a href="#aff0019" property="affiliation" typeof="Organization" role="doc-noteref">19</a></sup></span> ∙ <span property="author" typeof="Person" role="listitem"><a href="#au0015"><span property="givenName">Bruce L.</span> <span property="familyName">Levine</span></a><sup class="xref"><a href="#aff0020" property="affiliation" typeof="Organization" role="doc-noteref">20</a>,<a href="#fn2" role="doc-noteref">⁎⁎⁎</a></sup></span> on behalf of the <span property="author" typeof="Person" role="listitem"><a href="#au0016"><span property="name">ISCT Committee on the Ethics of Cell and Gene Therapy (ECGT)</span></a></span><span data-displayed-on="all"> … <span><span data-action="reveal">Show more</span></span> </span><span data-displayed-on="none" data-on-display="all" aria-hidden="true"> <span data-action="hide">Show less</span></span></span></span></div><div class="core-self-citation"><div id="core-affiliations-notes"><div class="affiliations"><div property="affiliation" typeof="Organization"><span class="label">1</span><span id="aff0001" property="name">Department of Oral Biology, University at Buffalo, The State University of New York, Buffalo, New York, USA</span></div><div property="affiliation" typeof="Organization"><span class="label">2</span><span id="aff0002" property="name">Cell, Gene and Tissue Engineering Center, University at Buffalo, The State University of New York, Buffalo, New York, USA</span></div><div property="affiliation" typeof="Organization"><span class="label">3</span><span id="aff0003" property="name">Andalusian Transplant Coordination, Servicio Andaluz de Salud; Sevilla, Spain</span></div><div property="affiliation" typeof="Organization"><span class="label">4</span><span id="aff0004" property="name">AdBio Partners, Paris, France</span></div><div property="affiliation" typeof="Organization"><span class="label">5</span><span id="aff0005" property="name">Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, Houston Methodist Hospital, Houston, Texas, USA</span></div><div property="affiliation" typeof="Organization"><span class="label">6</span><span id="aff0006" property="name">Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA</span></div><div property="affiliation" typeof="Organization"><span class="label">7</span><span id="aff0007" property="name">School of Public Policy, Georgia Institute of Technology, Atlanta, Georgia, USA</span></div><div property="affiliation" typeof="Organization"><span class="label">8</span><span id="aff0008" property="name">Melbourne Medical School, University of Melbourne, Parkville, Victoria, Australia</span></div><div property="affiliation" typeof="Organization"><span class="label">9</span><span id="aff0009" property="name">Murdoch Children's Research Institute, Parkville, Victoria, Australia</span></div><div property="affiliation" typeof="Organization"><span class="label">10</span><span id="aff0010" property="name">Gene and Stem Cell Therapy Program Centenary Institute, University of Sydney, Sydney, NSW, Australia</span></div><div property="affiliation" typeof="Organization"><span class="label">11</span><span id="aff0011" property="name">Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia</span></div><div property="affiliation" typeof="Organization"><span class="label">12</span><span id="aff0012" property="name">Cell & Molecular Therapies, Royal Prince Alfred Hospital, Camperdown, NSW, Australia</span></div><div property="affiliation" typeof="Organization"><span class="label">13</span><span id="aff0013" property="name">Department of Health, Society, and Behavior, Program in Public Health; Stem Cell Research Center; Institute for Clinical and Translational Science; Department of Family Medicine; University of California, Irvine; Irvine, California, USA</span></div><div property="affiliation" typeof="Organization"><span class="label">14</span><span id="aff0014" property="name">Stem Cell and Regenerative Medicine Research Department, Academic Center for Education, Culture and Research (ACECR)-Khorasan Razavi, Mashhad, Iran</span></div><div property="affiliation" typeof="Organization"><span class="label">15</span><span id="aff0015" property="name">Gastroenterology Unit, Department of Medicine, A.O.U.I. Policlinico G.B. Rossi & University of Verona, Verona, Italy</span></div><div property="affiliation" typeof="Organization"><span class="label">16</span><span id="aff0016" property="name">International Society for Cell & Gene Therapy, Vancouver, Canada</span></div><div property="affiliation" typeof="Organization"><span class="label">17</span><span id="aff0017" property="name">Department of Haematology, Christian Medical College, Ranipet Campus, Ranipet & Centre for Stem Cell Research (a unit of inStem Bengaluru) CMC Campus, Vellore, India</span></div><div property="affiliation" typeof="Organization"><span class="label">18</span><span id="aff0018" property="name">University of Vermont College of Medicine, Burlington, Vermont, USA</span></div><div property="affiliation" typeof="Organization"><span class="label">19</span><span id="aff0019" property="name">Moritz College of Law, Drug Enforcement and Policy Center, Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA</span></div><div property="affiliation" typeof="Organization"><span class="label">20</span><span id="aff0020" property="name">Center for Cellular Immunotherapies, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, Pennsylvania, USA</span></div></div><div class="core-authors-notes"><div role="doc-footnote" data-has="label"><div class="label">⁎⁎</div><div id="fn1"><div id="notep0001" role="paragraph">These authors have contributed equally to this work and should be considered second co-authors</div></div></div><div role="doc-footnote" data-has="label"><div class="label">⁎⁎⁎</div><div id="fn2"><div id="notep0002" role="paragraph">Senior author.</div></div></div></div></div><div id="core-content-info"><div class="history"><div>Publication History:</div><div><span>Received December 23, 2022</span>; <span>Accepted March 6, 2023</span></div></div><div class="core-links"><span class="doi">DOI: <a href="https://doi.org/10.1016/j.jcyt.2023.03.002" property="sameAs" target="_blank">10.1016/j.jcyt.2023.03.002</a></span><span class="science-direct">Also available on <a href="https://www.sciencedirect.com/science/article/pii/S1465324923000646" target="_blank">ScienceDirect</a></span></div><div role="paragraph">Copyright: © 2023 International Society for Cell & Gene Therapy. Published by Elsevier Inc.</div><div class="core-links"><span>User License: <a href="http://creativecommons.org/licenses/by-nc-nd/4.0/" target="_blank">Creative Commons Attribution – NonCommercial – NoDerivs (CC BY-NC-ND 4.0)</a> | <a href="https://www.elsevier.com/open-access" target="_blank">Elsevier's open access license policy</a></span></div><div class="core-crossmark-badge"><a data-target="crossmark" href="#" title="Check for updates on crossmark" data-doi="10.1016/j.jcyt.2023.03.002" data-id="article-info-crossmark" class="crossmark__link"><svg xmlns="http://www.w3.org/2000/svg" fill="none" viewBox="0 0 290 58" height="22px" role="presentation"><path fill="url(#horizontal_crossmark)" stroke="#948F8F" stroke-miterlimit="10" stroke-width=".75" d="M287 1H3a2 2 0 0 0-2 2v52a2 2 0 0 0 2 2h284a2 2 0 0 0 2-2V3a2 2 0 0 0-2-2Z"></path><path fill="#535353" d="M80.3 23.58a6.395 6.395 0 0 0-.55-1.43 3.92 3.92 0 0 0-2.19-1.86 5.099 5.099 0 0 0-1.71-.29 5 5 0 0 0-2.46.58 4.831 4.831 0 0 0-1.69 1.54 6.921 6.921 0 0 0-1 2.19 10.16 10.16 0 0 0 0 5 6.921 6.921 0 0 0 1 2.19 4.83 4.83 0 0 0 1.69 1.5 5 5 0 0 0 2.46.58 4.44 4.44 0 0 0 1.85-.36 4.12 4.12 0 0 0 1.38-1c.39-.436.695-.942.9-1.49A7.094 7.094 0 0 0 80.4 29h3a8.46 8.46 0 0 1-.69 2.92 7.179 7.179 0 0 1-1.59 2.29 7 7 0 0 1-2.35 1.49 8.14 8.14 0 0 1-3 .52 8.43 8.43 0 0 1-3.59-.74 7.88 7.88 0 0 1-2.69-2 9.001 9.001 0 0 1-1.69-3 11.41 11.41 0 0 1 0-7.23 9.001 9.001 0 0 1 1.69-3 8.001 8.001 0 0 1 2.69-2 8.3 8.3 0 0 1 3.59-.75 9.44 9.44 0 0 1 2.83.41c.866.242 1.68.642 2.4 1.18A6.229 6.229 0 0 1 82.65 21a6.66 6.66 0 0 1 .78 2.58H80.3ZM85.9 17.9h2.85v6.63h.05a4.15 4.15 0 0 1 1.56-1.46 4.61 4.61 0 0 1 2.31-.59 4.83 4.83 0 0 1 3.33 1.1 4.21 4.21 0 0 1 1.22 3.3v8.88H94.4v-8.13a3.51 3.51 0 0 0-.65-2.21 2.36 2.36 0 0 0-1.87-.69 3.1 3.1 0 0 0-1.3.26 2.821 2.821 0 0 0-1 .73A3.41 3.41 0 0 0 89 26.8a3.88 3.88 0 0 0-.23 1.33v7.63H85.9V17.9ZM102.47 30c-.002.491.069.98.21 1.45.131.448.348.866.64 1.23a3.08 3.08 0 0 0 1.08.84 3.543 3.543 0 0 0 1.55.31 3.431 3.431 0 0 0 2-.54c.541-.402.94-.966 1.14-1.61h2.7A5.349 5.349 0 0 1 109.7 35a5.715 5.715 0 0 1-1.74.85 7 7 0 0 1-2 .29 6.848 6.848 0 0 1-2.7-.5 5.577 5.577 0 0 1-2-1.4A5.953 5.953 0 0 1 100 32a8.748 8.748 0 0 1-.41-2.75 7.768 7.768 0 0 1 .44-2.61 6.67 6.67 0 0 1 1.25-2.17 5.863 5.863 0 0 1 4.56-2 5.79 5.79 0 0 1 2.74.64c.783.41 1.466.986 2 1.69a6.824 6.824 0 0 1 1.16 2.41c.264.905.352 1.852.26 2.79h-9.53Zm6.65-1.87a4.605 4.605 0 0 0-.29-1.3c-.148-.4-.368-.77-.65-1.09a3.22 3.22 0 0 0-1-.75 3 3 0 0 0-1.31-.29 3.431 3.431 0 0 0-1.36.26 3.108 3.108 0 0 0-1 .73 3.594 3.594 0 0 0-.7 1.09 3.798 3.798 0 0 0-.29 1.35h6.65-.05ZM122.88 27.15a2.666 2.666 0 0 0-1-1.81 3.14 3.14 0 0 0-2-.61c-.4.005-.798.07-1.18.19-.435.136-.83.376-1.15.7a3.92 3.92 0 0 0-.87 1.43 6.783 6.783 0 0 0-.35 2.39c.002.539.065 1.076.19 1.6.113.509.316.993.6 1.43.273.41.635.752 1.06 1a3 3 0 0 0 1.58.39 2.872 2.872 0 0 0 2.06-.77 3.596 3.596 0 0 0 1-2.18h2.85a6.26 6.26 0 0 1-1.91 3.86 5.83 5.83 0 0 1-4 1.34 6.61 6.61 0 0 1-2.69-.51 5.695 5.695 0 0 1-2-1.4 6.001 6.001 0 0 1-1.21-2.11 8.279 8.279 0 0 1-.41-2.65 8.987 8.987 0 0 1 .4-2.72 6.237 6.237 0 0 1 1.2-2.21 5.614 5.614 0 0 1 2-1.47 6.7 6.7 0 0 1 2.79-.54 7.801 7.801 0 0 1 2.14.29 5.634 5.634 0 0 1 1.8.86c.529.386.969.88 1.29 1.45a5 5 0 0 1 .6 2.07h-2.85l.06-.02ZM128.13 17.9H131V28l5.15-5.22h3.5l-5 4.75 5.42 8.17h-3.47l-4-6.27-1.6 1.7v4.63h-2.85V17.9h-.02ZM147.15 22.83h2.13v-1.08a5.505 5.505 0 0 1 .3-2c.161-.456.436-.862.8-1.18.33-.273.721-.462 1.14-.55.44-.094.89-.141 1.34-.14a8.158 8.158 0 0 1 2 .18v2.24a4.113 4.113 0 0 0-.59-.11 6.343 6.343 0 0 0-.74 0 1.74 1.74 0 0 0-1 .27 1.204 1.204 0 0 0-.41 1.08v1.33h2.42V25h-2.42v10.8h-2.85V25h-2.12v-2.17ZM162.23 36.1a6.999 6.999 0 0 1-2.76-.51 5.877 5.877 0 0 1-2-1.41 5.998 5.998 0 0 1-1.33-2.18 8.775 8.775 0 0 1 0-5.48 6.008 6.008 0 0 1 1.27-2.15 5.894 5.894 0 0 1 2-1.41A7.71 7.71 0 0 1 165 23a5.894 5.894 0 0 1 2 1.41 6.003 6.003 0 0 1 1.28 2.15c.585 1.78.585 3.7 0 5.48a5.99 5.99 0 0 1-3.28 3.54 7.002 7.002 0 0 1-2.77.52Zm0-2.25a3.268 3.268 0 0 0 1.65-.4c.447-.262.83-.621 1.12-1.05.304-.444.528-.938.66-1.46a6.581 6.581 0 0 0 0-3.31 4.416 4.416 0 0 0-.66-1.46 3.526 3.526 0 0 0-1.15-1 3.6 3.6 0 0 0-3.3 0 3.526 3.526 0 0 0-1.15 1 4.414 4.414 0 0 0-.66 1.46 6.558 6.558 0 0 0 0 3.31c.132.522.356 1.016.66 1.46a3.47 3.47 0 0 0 1.15 1.05 3.26 3.26 0 0 0 1.68.4ZM171.13 22.83h2.67v2.5c.097-.362.264-.701.49-1 .251-.341.547-.647.88-.91a4.404 4.404 0 0 1 1.14-.66 3.41 3.41 0 0 1 1.28-.25c.23-.013.46-.013.69 0h.39v2.79l-.61-.09a5.173 5.173 0 0 0-.61 0 3.278 3.278 0 0 0-1.36.29 3.131 3.131 0 0 0-1.11.85 4.171 4.171 0 0 0-.75 1.39 6 6 0 0 0-.28 1.9v6.15h-2.85V22.83h.03ZM198.22 35.75h-2.8V34a3.907 3.907 0 0 1-1.56 1.56 4.25 4.25 0 0 1-2.11.59 4.742 4.742 0 0 1-3.75-1.31 5.537 5.537 0 0 1-1.12-3.84v-8.2h2.85v7.92a3.503 3.503 0 0 0 .65 2.4 2.38 2.38 0 0 0 1.83.7 3.599 3.599 0 0 0 1.5-.27 2.66 2.66 0 0 0 1-.74c.259-.326.444-.705.54-1.11a5.79 5.79 0 0 0 .16-1.4v-7.5h2.85v12.95h-.04ZM201.3 22.83h2.7v1.75a3.523 3.523 0 0 1 1.72-1.58 5.568 5.568 0 0 1 2.33-.49 6.17 6.17 0 0 1 2.66.54 5.246 5.246 0 0 1 1.89 1.47c.515.65.899 1.394 1.13 2.19.257.87.385 1.773.38 2.68.001.851-.114 1.7-.34 2.52a6.568 6.568 0 0 1-1 2.16 5.002 5.002 0 0 1-4.21 2.06c-.419 0-.837-.036-1.25-.11a5.39 5.39 0 0 1-1.2-.36A4.737 4.737 0 0 1 205 35a3.567 3.567 0 0 1-.81-.91v6.45h-2.89V22.83Zm10 6.47c0-.574-.078-1.146-.23-1.7a4.606 4.606 0 0 0-.67-1.46 3.475 3.475 0 0 0-1.12-1 3.06 3.06 0 0 0-1.55-.39A3.141 3.141 0 0 0 205 26a5.518 5.518 0 0 0-1 3.3c-.004.611.077 1.22.24 1.81.138.523.38 1.012.71 1.44a3.55 3.55 0 0 0 1.14 1 3.242 3.242 0 0 0 1.54.35 3.18 3.18 0 0 0 1.65-.4c.438-.25.817-.59 1.11-1 .299-.44.513-.931.63-1.45a7.38 7.38 0 0 0 .23-1.75h.05ZM228.67 35.75H226V34a3.38 3.38 0 0 1-1.67 1.61 5.668 5.668 0 0 1-2.33.49 6.17 6.17 0 0 1-2.66-.54 5.307 5.307 0 0 1-1.89-1.46 6.254 6.254 0 0 1-1.12-2.19 9.48 9.48 0 0 1-.37-2.71 8.67 8.67 0 0 1 .47-3 6.058 6.058 0 0 1 1.26-2.1 4.89 4.89 0 0 1 1.8-1.21 5.738 5.738 0 0 1 2.06-.39c.412 0 .824.037 1.23.11.413.073.815.194 1.2.36.38.166.736.381 1.06.64.32.255.594.562.81.91V17.9h2.85v17.85h-.03Zm-10-6.33c-.001.55.069 1.098.21 1.63.13.511.35.996.65 1.43.288.414.668.757 1.11 1a3.241 3.241 0 0 0 1.6.38 3.199 3.199 0 0 0 1.64-.4 3.398 3.398 0 0 0 1.13-1.05c.297-.447.517-.94.65-1.46.14-.542.211-1.1.21-1.66a5.227 5.227 0 0 0-1-3.35 3.175 3.175 0 0 0-2.61-1.2 3.23 3.23 0 0 0-1.69.41 3.478 3.478 0 0 0-1.12 1.07 4.494 4.494 0 0 0-.62 1.5 7.871 7.871 0 0 0-.11 1.7h-.05ZM242.6 32.88c-.018.258.03.516.14.75a.577.577 0 0 0 .54.23h.3c.135-.002.269-.019.4-.05v2l-.39.11-.49.08-.5.08h-.42a2.75 2.75 0 0 1-1.45-.35 1.731 1.731 0 0 1-.75-1.23 4.998 4.998 0 0 1-2.09 1.2 8.224 8.224 0 0 1-2.39.38 5.861 5.861 0 0 1-1.67-.24 4.394 4.394 0 0 1-1.41-.7 3.35 3.35 0 0 1-1-1.18 3.624 3.624 0 0 1-.36-1.66 3.84 3.84 0 0 1 .44-2 3.246 3.246 0 0 1 1.15-1.17 5.195 5.195 0 0 1 1.6-.61c.593-.127 1.19-.223 1.79-.29a14.77 14.77 0 0 1 1.47-.21 6.896 6.896 0 0 0 1.24-.21c.318-.077.611-.236.85-.46a1.286 1.286 0 0 0 .31-.94 1.458 1.458 0 0 0-.26-.9A1.759 1.759 0 0 0 239 25a2.807 2.807 0 0 0-.86-.25 6.941 6.941 0 0 0-.9-.06 3.58 3.58 0 0 0-2 .5 2 2 0 0 0-.87 1.55h-2.85c.021-.73.227-1.442.6-2.07.338-.54.797-.996 1.34-1.33a5.475 5.475 0 0 1 1.84-.7c.692-.134 1.395-.2 2.1-.2.632 0 1.262.067 1.88.2a5.337 5.337 0 0 1 1.66.65 3.6 3.6 0 0 1 1.19 1.16c.314.525.47 1.129.45 1.74v6.65l.02.04Zm-2.85-3.6a3.45 3.45 0 0 1-1.6.51c-.667.06-1.3.147-1.9.26a6.137 6.137 0 0 0-.87.21 2.64 2.64 0 0 0-.75.38c-.22.164-.395.38-.51.63a2.129 2.129 0 0 0-.19.94c-.011.29.085.575.27.8.182.215.407.388.66.51.269.128.555.216.85.26.277.05.558.076.84.08a4.63 4.63 0 0 0 1-.12 3.418 3.418 0 0 0 1-.43 2.73 2.73 0 0 0 .81-.76 1.93 1.93 0 0 0 .32-1.14v-2.14l.07.01ZM244.37 22.83h2.15V19h2.85v3.88h2.58V25h-2.58v6.9a7.064 7.064 0 0 0 0 .77c.016.194.074.381.17.55a.84.84 0 0 0 .41.34 2 2 0 0 0 .75.11h.6c.203-.01.404-.04.6-.09v2.2l-.93.1a8.403 8.403 0 0 1-.92 0 6.33 6.33 0 0 1-1.81-.21 2.421 2.421 0 0 1-1.08-.62 2.15 2.15 0 0 1-.52-1 7.791 7.791 0 0 1-.16-1.42V25h-2.15v-2.17h.04ZM256.22 30c-.002.491.069.98.21 1.45.131.448.348.866.64 1.23a3.08 3.08 0 0 0 1.08.84 3.543 3.543 0 0 0 1.55.31 3.431 3.431 0 0 0 2-.54c.541-.402.94-.966 1.14-1.61h2.7a5.352 5.352 0 0 1-2.1 3.26 5.715 5.715 0 0 1-1.74.85 7 7 0 0 1-2 .29 6.848 6.848 0 0 1-2.7-.5 5.577 5.577 0 0 1-2-1.4 5.947 5.947 0 0 1-1.21-2.18 8.754 8.754 0 0 1-.41-2.75 7.758 7.758 0 0 1 .44-2.61 6.67 6.67 0 0 1 1.25-2.17 5.863 5.863 0 0 1 4.56-2 5.79 5.79 0 0 1 2.74.64c.783.41 1.466.986 2 1.69a6.824 6.824 0 0 1 1.16 2.41c.243.916.308 1.87.19 2.81h-9.5V30Zm6.65-1.87a4.605 4.605 0 0 0-.29-1.3c-.148-.4-.368-.77-.65-1.09a3.22 3.22 0 0 0-1-.75 3 3 0 0 0-1.31-.29 3.431 3.431 0 0 0-1.36.26 3.108 3.108 0 0 0-1 .73 3.575 3.575 0 0 0-.7 1.09 3.798 3.798 0 0 0-.29 1.35h6.65-.05ZM270 31.6a2.154 2.154 0 0 0 .95 1.75c.607.35 1.3.524 2 .5.304-.002.608-.022.91-.06a3.943 3.943 0 0 0 1-.24c.286-.105.54-.28.74-.51a1.23 1.23 0 0 0 .26-.89 1.261 1.261 0 0 0-.4-.9 2.779 2.779 0 0 0-1-.56 9.315 9.315 0 0 0-1.34-.36l-1.5-.33a14.219 14.219 0 0 1-1.54-.42 4.937 4.937 0 0 1-1.33-.68 3.12 3.12 0 0 1-.94-1.09 3.472 3.472 0 0 1-.35-1.64 2.94 2.94 0 0 1 .51-1.76 3.913 3.913 0 0 1 1.3-1.15 5.66 5.66 0 0 1 1.75-.61 10.316 10.316 0 0 1 1.84-.17 8.418 8.418 0 0 1 1.91.21 5.19 5.19 0 0 1 1.65.69c.496.318.916.741 1.23 1.24.341.559.55 1.188.61 1.84h-3a1.783 1.783 0 0 0-.94-1.37 3.892 3.892 0 0 0-1.69-.35 6.093 6.093 0 0 0-.71 0 3.327 3.327 0 0 0-.78.19 1.642 1.642 0 0 0-.61.4 1 1 0 0 0-.25.69 1.093 1.093 0 0 0 .36.85c.294.245.634.428 1 .54.437.153.885.274 1.34.36l1.55.33a20.9 20.9 0 0 1 1.53.42c.479.157.931.386 1.34.68.41.277.751.643 1 1.07.255.494.379 1.045.36 1.6a3.48 3.48 0 0 1-.52 2 4.15 4.15 0 0 1-1.36 1.3 6.19 6.19 0 0 1-1.86.73 9.435 9.435 0 0 1-2 .23 8.823 8.823 0 0 1-2.26-.27 5.265 5.265 0 0 1-1.8-.84 4 4 0 0 1-1.2-1.4 4.445 4.445 0 0 1-.46-2h2.7v-.02Z"></path><path fill="#C72914" d="m21.94 38.74 18.12-12.08v-14.5H21.94v26.58Z"></path><path fill="#EF3340" d="M40.06 38.74 21.94 26.66v-14.5h18.12v26.58Z"></path><path fill="#3EB1C8" d="M31 9a20 20 0 1 0 0 40 20 20 0 0 0 0-40Zm0 35.1a15.1 15.1 0 1 1 0-30.2 15.1 15.1 0 0 1 0 30.2Z"></path><path fill="#FFC72C" d="M42.09 39.23A15.09 15.09 0 0 1 17 23.38l-4.2-2.64a20 20 0 0 0 33.49 21.14l-4.2-2.65Z"></path><defs><linearGradient id="horizontal_crossmark" x1="145" x2="145" y1="7.33" y2="56.82" gradientUnits="userSpaceOnUse"><stop stop-color="#fff"></stop><stop offset="1" stop-color="#c4c4c4"></stop></linearGradient></defs></svg></a></div><div class="core-content-info"></div></div><div id="core-linked-content"> </div></div></div></header><div class="core-header-aside"><div class="article-header__download-full-issue"><button title="Download full issue" type="submit" formaction="/action/downloadMultiplePdf?action=downloadIssuePdf&journal=jcyt&volume=25&issue=9&pii=S1465-3249%2822%29X0022-4" class="btn--download-issue btn--cancel table-of-content__links--item download-full-issue"><i class="icon-download-new"></i><span>Download Full Issue</span></button><div class="table-of-content__alert table-of-content__alert--download"><p>Download started</p><a href="#" class="table-of-content__alert--close">Ok</a></div></div> <div class="cover-image cover-image--axel"><div class="cover-image__thumb"><a href="https://www.isct-cytotherapy.org/issue/S1465-3249(22)X0022-4"><img src="/cms/asset/8aba9f9a-672b-4711-a183-cfb1feb48ce7/cov200h.gif" alt="Cover Image - Cytotherapy, Volume 25, Issue 9"/></a></div></div> </div></div><div data-core-wrapper="content"><div data-core-nav="header" data-extent="frontmatter"><ul class="core-nav-wrapper core-container" role="menubar" aria-label="Article navigation"><li role="none" class="navigation-menu-pdf"> <div data-widget-id="b88e1592-f246-4733-9913-d71c9f598189" data-widget-name="UX3ArticleToolsWidget" class="article-tools"><a href="/action/showPdf?pii=S1465-3249%2823%2900064-6" title="Standard PDF (opens in a new tab)" target="_blank" aria-hidden="false" role="menuitem" class="article-tools__item__pdf"><svg focusable="false" viewBox="0 0 32 32" width="20" height="20" title="PDF" class="pdf-icon"><path id="pdfwhite" d="M7 .362h17.875l6.763 6.1V31.64H6.948V16z" stroke="#000" stroke-width=".703" fill="#fff"></path><path id="pdfda0000" d="M.167 2.592H22.39V9.72H.166z" fill="#da0000"></path><path id="pdffff9f9" fill="#fff9f9" d="M5.97 3.638h1.62c1.053 0 1.483.677 1.488 1.564.008.96-.6 1.564-1.492 1.564h-.644v1.66h-.977V3.64m.977.897v1.34h.542c.27 0 .596-.068.596-.673-.002-.6-.32-.667-.596-.667h-.542m3.8.036v2.92h.35c.933 0 1.223-.448 1.228-1.462.008-1.06-.316-1.45-1.23-1.45h-.347m-.977-.94h1.03c1.68 0 2.523.586 2.534 2.39.01 1.688-.607 2.4-2.534 2.4h-1.03V3.64m4.305 0h2.63v.934h-1.657v.894H16.6V6.4h-1.56v2.026h-.97V3.638"></path><path id="pdff91d0a" d="M19.462 13.46c.348 4.274-6.59 16.72-8.508 15.792-1.82-.85 1.53-3.317 2.92-4.366-2.864.894-5.394 3.252-3.837 3.93 2.113.895 7.048-9.25 9.41-15.394zM14.32 24.874c4.767-1.526 14.735-2.974 15.152-1.407.824-3.157-13.72-.37-15.153 1.407zm5.28-5.043c2.31 3.237 9.816 7.498 9.788 3.82-.306 2.046-6.66-1.097-8.925-4.164-4.087-5.534-2.39-8.772-1.682-8.732.917.047 1.074 1.307.67 2.442-.173-1.406-.58-2.44-1.224-2.415-1.835.067-1.905 4.46 1.37 9.065z" fill="#f91d0a"></path></svg><span class="basic">Download PDF</span><span class="alternative">Download PDF</span></a></div> </li><li role="none"><button data-id="article-toolbar-showhide" aria-controls="article_sections_menu" aria-expanded="false" aria-haspopup="true" aria-label="Toggle section navigation menu" role="menuitem"><i class="icon-list" aria-hidden="true"></i><span>Outline</span></button><nav id="article_sections_menu" role="menu" aria-label="Contents" data-core-nav="article"><ul role="group"><li role="none"><a role="menuitem" href="#author-abstract">Abstract</a></li><li role="none"><a role="menuitem" href="#keywords">Keywords</a></li><li role="none"><a role="menuitem" href="#sec-1">Introduction</a></li><li role="none"><a role="menuitem" href="#sec-2">Features of Unproven Interventions (Including Tokens of Legitimacy)</a></li><li role="none"><a role="menuitem" href="#sec-3">Approved and Proven CGT Products</a></li><li role="none"><a role="menuitem" href="#sec-4">Levels of Evidence Required for Widespread Approval</a></li><li role="none"><a role="menuitem" href="#sec-5">Reporting Mechanisms in the United States and Worldwide</a></li><li role="none"><a role="menuitem" href="#sec-6">Actions ISCT Members Can Take to Address Direct-to-Consumer Marketing of Unproven CGTs</a></li><li role="none"><a role="menuitem" href="#sec-7">Conclusions</a></li><li role="none"><a role="menuitem" href="#sec-8">Author Contributions</a></li><li role="none"><a role="menuitem" href="#conflict">Declaration of Competing Interest</a></li><li role="none"><a role="menuitem" href="#acknowledgments">Acknowledgments</a></li><li role="none"><a role="menuitem" href="#references">References</a></li></ul></nav></li><li role="none" class="navigation-menu-share"> <script type="text/javascript" defer="defer" src="https://static.addtoany.com/menu/page.js"></script><script>var a2a_config = a2a_config || {}; let res = window.location.href.replace(/$/g, "%28").replace(/$/g, "%29"); a2a_config.templates = a2a_config.templates || {}; a2a_config.templates.email = { body: res }; </script><div data-widget-id="9a0a26e7-03bd-4d47-8984-9e7fa650db97" data-widget-name="UX3share" aria-hidden="false" role="group" class="article-tools__dropblock article-tools__share"><button aria-label="Toggle share menu" aria-expanded="false" aria-haspopup="true" role="menuitem" aria-controls="navigation_menu_share_block" aria-labelledby="share-label" class="article-tools__item__share"><i aria-hidden="true" class="icon-article-share"></i><span id="share-label">Share</span></button><div id="navigation_menu_share_block" role="menu" class="share__block axel-share article-tools__dropblock__holder"><h4 class="axel-share__title heading">Share<button title="Close share menu" aria-expanded="false" aria-haspopup="true" aria-controls="navigation_menu_share_block"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 70 128" height="24" width="14"><path d="M68.94 36.12L62 29 35 56 8 29l-7 7 27 27L1 90l7 7 27-27 27 27 7-7-27-27 26.94-26.88"></path></svg></button></h4><div class="axel-share__inner"><span class="sr-only">Share on</span><ul class="a2a__share-list rlist w-slide--list a2a a2a_kit a2a_kit_size_32 a2a_default_style" data-a2a-url="https://www.isct-cytotherapy.org/article/S1465-3249%2823%2900064-6/fulltext"><li class="a2a_listitem_custom"><a role="link" title="Email" class="a2a_button_email"><i aria-hidden="true" class="at-icon-wrapper icon-gizmo-email-plus"></i><span>Email</span></a></li><li class="a2a_listitem_custom"><a role="link" title="formerly known as Twitter" class="a2a_button_twitter"><i aria-hidden="true" class="at-icon-wrapper icon-x-default"></i><span>X</span></a></li><li class="a2a_listitem_custom"><a role="link" title="Facebook" class="a2a_button_facebook"><i aria-hidden="true" class="at-icon-wrapper icon-facebook-square-2"></i><span>Facebook</span></a></li><li class="a2a_listitem_custom"><a role="link" title="LinkedIn" class="a2a_button_linkedin"><i aria-hidden="true" class="at-icon-wrapper icon-linkedin-square"></i><span>LinkedIn</span></a></li><li class="a2a_listitem_custom"><a role="link" title="Sina Weibo" class="a2a_button_sina_weibo"><i aria-hidden="true" class="at-icon-wrapper icon-weibo"></i><span>Sina Weibo</span></a></li><li class="a2a_listitem_custom"><a role="link" title="Add to Mendeley" class="a2a_button_mendeley"><i aria-hidden="true" class="at-icon-wrapper icon-mendeley-2"></i><span>Add to Mendeley</span></a></li></ul><div class="extra-links-drop-zone"> <div data-widget-id="8290640f-f974-44c3-b07b-10ae0de3a777" data-widget-name="UX3HTMLWidget"><a class="axel-share__extra" target="_blank" href="/personalize/addFavoritePublication?doi=10.1016/j.jcyt.2023.03.002"> <i class="icon-reading-list" aria-hidden="true"></i> <span>Add to my reading list</span> </a></div> </div></div></div></div> </li><li role="none"><button data-id="article-nav-menubar-more" aria-controls="article_more_menu" aria-expanded="false" aria-haspopup="true" aria-label="Toggle more menu" role="menuitem"><i aria-hidden="true" class="icon-more-mobile"></i><span>More</span></button><div class="info-panel"><div role="menuitem" class="info-panel__left-content"><div class="info-panel__article_tools info-panel__item"><div id="article_more_menu" aria-label="More menu" data-core-nav="more"><div class="heading">More<button title="Close more menu" aria-controls="article_more_menu" aria-haspopup="true"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 70 128" height="24" width="14"><path d="M68.94 36.12L62 29 35 56 8 29l-7 7 27 27L1 90l7 7 27-27 27 27 7-7-27-27 26.94-26.88"></path></svg></button></div> <ul data-widget-id="456b8a45-7ff3-433c-b2f1-84eabc846406" data-widget-name="UX3ArticleToolsWidget" class="article-tools"><li class="article-tools__item article-tools__pdf"><a href="/action/showPdf?pii=S1465-3249%2823%2900064-6" title="Standard PDF (opens in a new tab)" target="_blank" aria-hidden="false" class="article-tools__ctrl article-tools__item__pdf"><svg focusable="false" viewBox="0 0 32 32" width="20" height="20" title="PDF" class="pdf-icon"><path id="pdfwhite" d="M7 .362h17.875l6.763 6.1V31.64H6.948V16z" stroke="#000" stroke-width=".703" fill="#fff"></path><path id="pdfda0000" d="M.167 2.592H22.39V9.72H.166z" fill="#da0000"></path><path id="pdffff9f9" fill="#fff9f9" d="M5.97 3.638h1.62c1.053 0 1.483.677 1.488 1.564.008.96-.6 1.564-1.492 1.564h-.644v1.66h-.977V3.64m.977.897v1.34h.542c.27 0 .596-.068.596-.673-.002-.6-.32-.667-.596-.667h-.542m3.8.036v2.92h.35c.933 0 1.223-.448 1.228-1.462.008-1.06-.316-1.45-1.23-1.45h-.347m-.977-.94h1.03c1.68 0 2.523.586 2.534 2.39.01 1.688-.607 2.4-2.534 2.4h-1.03V3.64m4.305 0h2.63v.934h-1.657v.894H16.6V6.4h-1.56v2.026h-.97V3.638"></path><path id="pdff91d0a" d="M19.462 13.46c.348 4.274-6.59 16.72-8.508 15.792-1.82-.85 1.53-3.317 2.92-4.366-2.864.894-5.394 3.252-3.837 3.93 2.113.895 7.048-9.25 9.41-15.394zM14.32 24.874c4.767-1.526 14.735-2.974 15.152-1.407.824-3.157-13.72-.37-15.153 1.407zm5.28-5.043c2.31 3.237 9.816 7.498 9.788 3.82-.306 2.046-6.66-1.097-8.925-4.164-4.087-5.534-2.39-8.772-1.682-8.732.917.047 1.074 1.307.67 2.442-.173-1.406-.58-2.44-1.224-2.415-1.835.067-1.905 4.46 1.37 9.065z" fill="#f91d0a"></path></svg><span class="basic">Download PDF</span><span class="alternative">Download PDF</span></a></li><li><a href="https://www.isct-cytotherapy.org/action/showCitFormats?doi=10.1016%2Fj.jcyt.2023.03.002&pii=S1465-3249%2823%2900064-6" title="Cite" target="_blank" aria-label="Open Cite in new tab" class="article-tools__item__displayExportCitation"><i aria-hidden="true" class="icon-export-Citation"></i><span>Cite</span></a></li><li id="article_tools_share"> <script type="text/javascript" defer="defer" src="https://static.addtoany.com/menu/page.js"></script><script>var a2a_config = a2a_config || {}; let res = window.location.href.replace(/$/g, "%28").replace(/$/g, "%29"); a2a_config.templates = a2a_config.templates || {}; a2a_config.templates.email = { body: res }; </script><div data-widget-id="eb69bac3-4f48-4142-a6e4-3ba1b70e518e" data-widget-name="UX3share" class="dropBlock article-tools__dropblock article-tools__share"><a href="#" data-db-target-for="eb69bac3-4f48-4142-a6e4-3ba1b70e518e" aria-expanded="false" title="open Share menu" aria-labelledby="share-label-523" class="article-tools__ctrl share__ctrl"><i aria-hidden="true" class="icon-article-share"></i><span id="share-label-523">Share</span></a><div data-db-target-of="eb69bac3-4f48-4142-a6e4-3ba1b70e518e" id="eb69bac3-4f48-4142-a6e4-3ba1b70e518e_Pop" class="share__block axel-share dropBlock__holder article-tools__dropblock__holder"><h4 class="axel-share__title">Share</h4><div class="axel-share__inner"><span class="sr-only">Share on</span><ul class="a2a__share-list rlist w-slide--list a2a a2a_kit a2a_kit_size_32 a2a_default_style" data-a2a-url="https://www.isct-cytotherapy.org/article/S1465-3249%2823%2900064-6/fulltext"><li class="a2a_listitem_custom"><a role="link" title="Email" class="a2a_button_email"><i aria-hidden="true" class="at-icon-wrapper icon-gizmo-email-plus"></i><span>Email</span></a></li><li class="a2a_listitem_custom"><a role="link" title="formerly known as Twitter" class="a2a_button_twitter"><i aria-hidden="true" class="at-icon-wrapper icon-x-default"></i><span>X</span></a></li><li class="a2a_listitem_custom"><a role="link" title="Facebook" class="a2a_button_facebook"><i aria-hidden="true" class="at-icon-wrapper icon-facebook-square-2"></i><span>Facebook</span></a></li><li class="a2a_listitem_custom"><a role="link" title="LinkedIn" class="a2a_button_linkedin"><i aria-hidden="true" class="at-icon-wrapper icon-linkedin-square"></i><span>LinkedIn</span></a></li><li class="a2a_listitem_custom"><a role="link" title="Sina Weibo" class="a2a_button_sina_weibo"><i aria-hidden="true" class="at-icon-wrapper icon-weibo"></i><span>Sina Weibo</span></a></li><li class="a2a_listitem_custom"><a role="link" title="Add to Mendeley" class="a2a_button_mendeley"><i aria-hidden="true" class="at-icon-wrapper icon-mendeley-2"></i><span>Add to Mendeley</span></a></li></ul><div class="extra-links-drop-zone"> <div data-widget-id="602ee1d1-9bea-40c0-9a1e-af73ceca37a1" data-widget-name="UX3HTMLWidget"><a class="axel-share__extra" target="_blank" href="/personalize/addFavoritePublication?doi=10.1016/j.jcyt.2023.03.002"> <i class="icon-reading-list" aria-hidden="true"></i> <span>Add to my reading list</span> </a></div> </div></div></div></div> </li><li><a href="https://www.isct-cytotherapy.org/action/addCitationAlert?doi=10.1016%2Fj.jcyt.2023.03.002" title="Set Alert" target="_blank" aria-label="Open Set Alert in new tab" class="article-tools__item__displayCreateCitationAlert"><i aria-hidden="true" class="icon-set-alert"></i><span>Set Alert</span></a></li><li><a href="https://s100.copyright.com/AppDispatchServlet?publisherName=ELS&contentID=S1465324923000646&orderBeanReset=true&orderSource=Phoenix" title="Get Rights" target="_blank" aria-label="Open Get Rights in new tab" class="article-tools__item__request"><i aria-hidden="true" class="icon-get-rights"></i><span>Get Rights</span></a></li><li><a href="http://www.medreprints.com/?pii=S1465324923000646&issn=14653249&source=jbs" title="Reprints" target="_blank" aria-label="Open Reprints in new tab" class="article-tools__item__reprints"><i aria-hidden="true" class="icon-article-reprints"></i><span>Reprints</span></a></li></ul> </div></div><div class="info-panel__download-issue info-panel__item"><div class="article-header__download-full-issue"><button title="Download full issue" type="submit" formaction="/action/downloadMultiplePdf?action=downloadIssuePdf&journal=jcyt&volume=25&issue=9&pii=S1465-3249%2822%29X0022-4" class="btn--download-issue btn--cancel table-of-content__links--item download-full-issue"><i class="icon-download-new"></i><span>Download Full Issue</span></button><div class="table-of-content__alert table-of-content__alert--download"><p>Download started</p><a href="#" class="table-of-content__alert--close">Ok</a></div></div></div></div><div class="info-panel__right-content"><div class="info-panel__navigation info-panel__item"><div role="none" class="content-navigation"><a href="/article/S1465-3249(23)00951-9/fulltext" role="menuitem" aria-label="Previous article" aria-disabled="false" class="content-navigation__prev"><i aria-hidden="true" class="icon-arrow_l"></i><span>Previous article</span></a><a href="/article/S1465-3249(23)00957-X/fulltext" role="menuitem" aria-label="Next article" aria-disabled="false" class="content-navigation__next"><span>Next article</span><i aria-hidden="true" class="icon-arrow_r"></i></a></div></div></div></div></li></ul></div><div><div class="core-content-inner"><div class="core-linked-content"></div><div id="abstracts" data-extent="frontmatter"><div class="core-container"><section id="author-abstract" property="abstract" typeof="Text" role="doc-abstract"><h2 property="name">Abstract</h2><div id="spara006" role="paragraph">The field of regenerative medicine, including cellular immunotherapies, is on a remarkable growth trajectory. Dozens of cell-, tissue- and gene-based products have received marketing authorization worldwide while hundreds-to-thousands are either in preclinical development or under clinical investigation in phased clinical trials. However, the promise of regenerative therapies has also given rise to a global industry of direct-to-consumer offerings of prematurely commercialized cell and cell-based products with unknown safety and efficacy profiles. Since its inception, the International Society for Cell & Gene Therapy Committee on the Ethics of Cell and Gene Therapy has opposed the premature commercialization of unproven cell- and gene-based interventions and supported the development of evidence-based advanced therapy products. In the present Guide, targeted at International Society for Cell & Gene Therapy members, we analyze this industry, focusing in particular on distinctive features of unproven cell and cell-based products and the use of tokens of scientific legitimacy as persuasive marketing devices. We also provide an overview of reporting mechanisms for patients who believe they have been harmed by administration of unapproved and unproven products and suggest practical strategies to address the direct-to-consumer marketing of such products. Development of this Guide epitomizes our continued support for the ethical and rigorous development of cell and cell-based products with patient safety and therapeutic benefit as guiding principles.</div></section></div></div><div class="core-linked-content"></div><section id="keywords" property="keywords"><h2>Keywords</h2><ol><li><a href="/action/doSearch?AllField="cell+and+gene+therapies+%28CGTs%29"&journalCode=jcyt" alt="Search on this keyword">cell and gene therapies (CGTs)</a></li><li><a href="/action/doSearch?AllField="regulatory+agencies"&journalCode=jcyt" alt="Search on this keyword">regulatory agencies</a></li><li><a href="/action/doSearch?AllField="reporting+mechanisms"&journalCode=jcyt" alt="Search on this keyword">reporting mechanisms</a></li><li><a href="/action/doSearch?AllField="tokens+of+scientific+legitimacy"&journalCode=jcyt" alt="Search on this keyword">tokens of scientific legitimacy</a></li><li><a href="/action/doSearch?AllField="unproven+cell+and+gene+interventions"&journalCode=jcyt" alt="Search on this keyword">unproven cell and gene interventions</a></li></ol></section><div class="core-linked-content"></div><div class="core-linked-content"></div><div class="core-linked-content"></div><section id="bodymatter" data-extent="bodymatter" property="articleBody" typeof="Text"><div class="core-container"><div id="para9001" role="paragraph"><div class="figure-wrap"><figure id="box1" class="boxed-text"><figcaption><div class="heading"><b>Box 1</b></div></figcaption><div id="para0003" role="paragraph">Regardless of outcome, patients, family members and physicians who believe they have experienced or witnessed deceptive, unethical practices, been mistreated or, sadly, suffered negative consequences from treatment should:<div id="celist0002" role="list"><div id="celistitem0111" role="listitem"><div class="label">–</div><div class="content"><div id="para0116" role="paragraph">inform their state/local jurisdictional physician licensing agency;</div></div></div><div id="celistitem0023" role="listitem"><div class="label">–</div><div class="content"><div id="para0218" role="paragraph">inform their state/local jurisdictional Department of Health and Consumer Affairs; and</div></div></div><div id="celistitem0033" role="listitem"><div class="label">–</div><div class="content"><div id="para0418" role="paragraph">inform their National Competent Authority or Authorities and National Consumer Protections Bureau(s).</div></div></div></div></div></figure></div></div><section id="sec-1"><h2>Introduction</h2><div id="para0007" role="paragraph">Two decades ago, businesses began advertising purported stem cell treatments on a direct-to-consumer basis for myriad indications. More recently, similar advertisements for purported gene therapy or extracellular vesicle treatments have also arisen. This phenomenon persists today, with a global marketplace of clinics selling putative advanced medicinal therapies without substantive evidence of safety and/or efficacy. This occurs under a number of different guises. Some clinics claim that the supposed advanced products they are selling are indeed safe and effective. Other businesses acknowledge the investigational nature of what they are selling but charge patients to access advanced products in pay-to-participate studies. These purported studies are generally poorly designed, unblinded, unrandomized and uncontrolled; typically, they have not been reviewed and authorized by national regulators. The International Society for Cell & Gene Therapy (ISCT), along with peer scientific organizations and patient advocacy groups, has played an important role in opposing the premature commercialization of unproven cell- and gene-based interventions and supporting the development of evidence-based, safe, and efficacious advanced medicinal products. The ISCT and other groups have also worked toward better regulation of cell and gene therapy investigations to assist the US Food & Drug Administration (FDA) and other regulatory bodies crack down on businesses offering unproven cell and gene therapies. The goal of ISCT and peer scientific organizations is to advocate for patient safety and access to new therapies by supporting clinical translational processes and corresponding regulatory paths developed to generate robust safety and efficacy data before products are commercialized. In particular, rigorous evaluation by national regulators of the benefit-to-risk balance for each individual product increases the likelihood that only safe and effective cell- and gene-based products enter the commercial marketplace.</div><div id="para0008" role="paragraph">In this guide for ISCT members, the ISCT Committee on the Ethics of Cell and Gene Therapy provides background and suggested strategies to counteract the direct-to-consumer marketing of unproven and unapproved cell-based, cell-derived and gene-based interventions. For the purposes of the Members Guide, cell-based, cell-derived and gene-based therapies/interventions will herein be consolidated under the term “CGT.” The purpose of this document is to address in an accessible manner the problematic scientific, ethical and legal concerns inherent in direct-to-consumer promotion of prematurely commercialized CGTs. The Guide also identifies additional resources that ISCT members might wish to consult to explore this subject in greater detail, including the 2015 ISCT comprehensive reference guide “Talking about Unproven Cell-Based Interventions” <a id="crf0030" href="#bib0001" role="doc-biblioref" data-xml-rid="bib0001">[1]</a>. The Guide begins by identifying common and recognizable features of unproven CGTs. Although there are variations in how such products reach the marketplace and are commercialized, it is common for them to be advertised and administered without a clear scientific rationale, sufficient pre-clinical data to support their use in patients, convincing safety and efficacy data generated in properly controlled clinical trials and/or standardized and reliable methods to confirm product quality and consistency.</div><div id="para0009" role="paragraph">The Guide further identifies other common characteristics of unproven CGTs. These include various strategies that businesses use to make unproven CGTs appear scientific and evidence-based. One prominent strategy is the use of “tokens of legitimacy” to make unproven products seem science-based, subject to appropriate oversight and ready for clinical deployment (<a id="crf0031" href="#tbl0001">Table 1</a>) <a id="crf0032" href="#bib0002" role="doc-biblioref" data-xml-rid="bib0002 bib0003 bib0004">[2–4]</a>. ISCT members, patients, families, caregivers, research participants and other relevant parties must be educated on how to identify such tokens of legitimacy and how they are often used to convince patients that CGT products are safe and effective in the absence of sufficient safety and efficacy data <a id="crf0034" href="#bib0005" role="doc-biblioref" data-xml-rid="bib0005">[5]</a>.</div><div class="figure-wrap"><figure id="tbl0001" class="table" data-figureviewer-ignore="true"><div class="table-wrap"><table data-figureviewer-ignore="true"><tbody><tr><td id="en0001">Reference to the websites of academic or industry researchers at reputable research institutions to suggest these scientists or their research support the unproven cell-based treatment</td></tr><tr><td id="en0002">Reference to articles from other research groups presenting pre-clinical or clinical research that appears related but do not directly address the marketed unproven intervention <a id="crf0086" href="#bib0002" role="doc-biblioref" data-xml-rid="bib0002">[2]</a></td></tr><tr><td id="en0003">Claims of institutional ethics committee review and approval (e.g., institutional review board approval in the United States) for so-called experimental “studies”</td></tr><tr><td id="en0004">Registering research on the US federal database ClinicalTrials.gov [<a id="crf0087" href="#bib0003" role="doc-biblioref" data-xml-rid="bib0003">3</a>,<a id="crf0088" href="#bib0004" role="doc-biblioref" data-xml-rid="bib0004">4</a>], or applying for patent protection of unproven “treatment approaches”</td></tr><tr><td id="en0005">Use of scientific advisory boards</td></tr></tbody></table></div><figcaption><span class="heading">Table 1</span><div id="spara001" role="paragraph">Tokens of scientific legitimacy.</div><div class="core-table-tools"><ul><li><a class="core-table-show-action" href="/action/showFullTableHTML?isHtml=true&tableId=tbl0001&pii=S1465-3249%2823%2900064-6" target="_blank">Open table in a new tab</a></li></ul></div></figcaption></figure></div><div id="para0010" role="paragraph">Next, the Guide provides insight into what constitutes evidence-based CGT products. There are cell- or gene-therapy based products that have been carefully tested in rigorously designed and conducted clinical trials and that subsequently have received pre-marketing authorization by national regulatory bodies. It is thus critically important to distinguish such evidence-based and approved therapies from products lacking evidence and regulatory approval. The Guide helps readers differentiate such products from one another and better understand why some products have obtained pre-marketing authorization. In brief, convincing, or substantial, evidence of safety and efficacy is typically required by regulatory bodies responsible for reviewing CGT products submitted for pre-marketing authorization. The Guide reviews what levels of evidence typically are required to obtain marketing approval and addresses how to determine when such evidence is absent or deficient.</div><div id="para0011" role="paragraph">Many patients and their caregivers, as well as clinicians and scientists, do not have framework for what to do if a business is advertising potentially risky unproven CGTs or when there is reason to think that a recipient of an unproven CGT product has been harmed as a result of being administered such an intervention. The Guide identifies reporting mechanisms for ISCT members, patients and other parties to report possible adverse events associated with such products or what may be problematic marketing practices or clinical activities. Although reporting mechanisms differ across jurisdictions, many national regulatory bodies offer online tools that patients and clinicians can use to report adverse events or concerning marketing activities associated with the sale and administration of unproven CGT products. Resources that enable such reporting may be provided from various regulatory and professional bodies. Regulatory bodies responsible for enforcing laws requiring honest advertising practices and consumer protection agencies may provide recourse for deceptive advertising claims. Medical boards and colleges are responsible for regulating the practice of physicians and other licensed health care professionals and may provide tools for reporting physician practices related to unproven CGTs. Drug regulatory agencies also provide mechanisms to report provision of unlicensed cell- or gene-based interventions and/or resulting adverse effects. The Guide provides insight into how to find and use a variety of such reporting tools. Finally, the Guide describes additional steps ISCT members and other concerned parties can take to contest direct-to-consumer marketing of unproven cell and gene interventions and support careful and rigorous evidence-based clinical translation of proven CGTs.</div><div id="para0012" role="paragraph">The Guide is not intended to serve as an exhaustive analysis of the various topics it covers. Rather, it is meant to provide an accessible overview that ISCT members can then supplement with additional resources identified in the Guide. This Guide embodies ISCT's continued support for developing CGT products in a rigorous and evidence-based manner that complies with ethical, legal and scientific standards for research and clinical translation of cell-based products and gene therapies.</div></section><section id="sec-2"><h2>Features of Unproven Interventions (Including Tokens of Legitimacy)</h2><div id="para0013" role="paragraph">CGT products may fall into various categories depending on their regulatory status and level of evidence supporting their use. First, some CGT-based interventions are evidence-based and licensed for use. Other interventions are evidence-based and do not require pre-marketing authorization. Yet, there is a large direct-to-consumer marketplace in which a wide variety of unproven CGT products are currently marketed and promoted without the appropriate regulatory authorization and oversight. Several types of CGTs that are currently offered commercially are unsupported by convincing evidence of safety and efficacy and can justifiably be described as unproven interventions. This means that they are potentially unsafe and there is little or no evidence to support claims that they will have meaningful therapeutic effects. In some cases, these interventions may be based on pre-clinical data that may show promise but is yet to be evaluated in well-designed and properly conducted clinical studies. Instead, these interventions are prematurely marketed directly to patients and requiring patients to pay for these interventions, rather than being offered through clinical trials or judicious use of non-trial preapproval access pathways (such as expanded access). This practice puts patients at risk and limits the opportunity to gather useful data on these interventions. In other cases, CGT-based interventions are offered directly to patients in the absence of even appropriate pre-clinical data, risking patients’ health and their financial resources with little-to-no reason to expect benefit from the intervention.</div><div id="para0014" role="paragraph">Examples of such interventions unsupported by data include cell-based products, cell-derived products such as extracellular vesicles and perinatal tissue products and rarely gene-based therapies including gene-modified cell therapies. These products continue to be promoted as purported treatments for a number of conditions, ranging from musculoskeletal diseases and injuries to neurological disorders (Parkinson's and Alzheimer's disease, cerebral palsy) and respiratory diseases (pulmonary fibrosis, chronic obstructive pulmonary disease).</div><div id="para0015" role="paragraph">The ISCT has previously defined the hallmarks of unproven cell-based therapies that can be readily applied to other types of cell-based or cell-derived or gene therapy products or services [<a id="crf0035" href="#bib0006" role="doc-biblioref" data-xml-rid="bib0006">6</a>,<a id="crf0036" href="#bib0007" role="doc-biblioref" data-xml-rid="bib0007">7</a>]. Unproven cell-based interventions typically meet some or all of the following criteria:<div id="celist0001" role="list"><div id="celistitem0001" role="listitem"><div class="label">•</div><div class="content"><div id="para0016" role="paragraph">unclear scientific rationale to suggest potential efficacy;</div></div></div><div id="celistitem0002" role="listitem"><div class="label">•</div><div class="content"><div id="para0017" role="paragraph">lack of understanding on the mechanism of action and/or the biological function to support clinical use;</div></div></div><div id="celistitem0003" role="listitem"><div class="label">•</div><div class="content"><div id="para0018" role="paragraph">insufficient data from <i>in vitro</i> assays, animal models and/or clinical studies regarding the safety profile to support the use in patients;</div></div></div><div id="celistitem0004" role="listitem"><div class="label">•</div><div class="content"><div id="para0019" role="paragraph">lack of a standardized approach to confirm product quality and ensure consistency in cell manufacturing based on adherence to mandatory guidelines;</div></div></div><div id="celistitem0005" role="listitem"><div class="label">•</div><div class="content"><div id="para0020" role="paragraph">inadequate information disclosed to patients to enable proper informed consent;</div></div></div><div id="celistitem0006" role="listitem"><div class="label">•</div><div class="content"><div id="para0021" role="paragraph">use within non-standardized or non-validated administration methods;</div></div></div><div id="celistitem0007" role="listitem"><div class="label">•</div><div class="content"><div id="para0022" role="paragraph">uncontrolled experimental procedures in humans;</div></div></div><div id="celistitem0008" role="listitem"><div class="label">•</div><div class="content"><div id="para0023" role="paragraph">supervision, review and approval by competent government organizations is lacking; and</div></div></div><div id="celistitem0009" role="listitem"><div class="label">•</div><div class="content"><div id="para0024" role="paragraph">payment, often of exorbitant fees, for experimental treatments or for participation in so-called clinical studies (“pay-to-participate”).</div></div></div></div></div><div id="para0025" role="paragraph">This list of potential “red flags” can be used as practical guidance by patients, families and caregivers trying to assess the legitimacy of offered CGT products.</div><div id="para0026" role="paragraph">In the absence of clinical trial data to establish safety and efficacy, unproven CGT-based interventions are often marketed through patient testimonials, celebrity endorsements and other tools of persuasion. Clinic websites may include positive statements purportedly obtained from patients or contain videos featuring patients discussing improvements that they claim resulted from the marketed intervention. While these testimonials often seem compelling, they are, even if believed to be accurate by the patient, problematic for use in medical decision-making. In addition, their veracity is often in question, for a variety of reasons, further limiting their utility. First, it is impossible to know whether the purported benefits, either transient or long-term, result from CGT administration. This includes placebo effects, which may play a role in any given patient's sense of improvement. Second, patients may have been paid or offered discounts on procedures in exchange for providing positive statements. In any case, evidence-based medical treatments cannot rely on anecdotal cases but are developed on the consistency of results following a standardized procedure that has to be authorized, supervised and evaluated by regulatory bodies.</div><div id="para0027" role="paragraph">Another common characteristic of unproven CGT-based interventions is the supposed ability of the same treatment approach to help patients with many different and unrelated conditions. Cells, particularly purported “stem cells,” are sometimes claimed to have special abilities to seek out and repair damaged tissues in such a manner that the same unproven intervention could potentially help patients with conditions ranging from neurological disorders to male-pattern baldness. These broad claims of efficacy across unrelated conditions do not align with established CGTs nor with those under legitimate clinical investigation and may be a useful indicator of clinics offering interventions not supported by appropriate evidence.</div><div id="para0028" role="paragraph">These unproven interventions are often marketed in a manner that appears to suggest they are supported by stronger scientific evidence than exists. These marketing strategies are collectively referred to as “tokens of scientific legitimacy” (<a id="crf0037" href="#tbl0001">Table 1</a>), and they have been discussed in the literature <a id="crf0038" href="#bib0008" role="doc-biblioref" data-xml-rid="bib0008 bib0009 bib0010">[8–10]</a>. Although each of these might be a characteristic of legitimate clinical research, none on its own provides sufficient evidence to establish a novel therapy as safe and effective. Their widespread use in direct-to-consumer advertising makes it more difficult for patients, families or caregivers considering their treatment options to assess if these interventions are appropriate. As a result, these tokens may mislead some patients into choosing unproven interventions without fully understanding the extent to which they are unproven rather than supported by appropriate scientific evidence.</div><div id="para0029" role="paragraph">Patients considering their medical options, as well as clinicians and others involved in the development of CGTs that may be called on to offer advice to patients, should be aware of the various marketing tactics and tokens of legitimacy commonly used by providers of unproven cell and gene therapies.</div></section><section id="sec-3"><h2>Approved and Proven CGT Products</h2><div id="para0030" role="paragraph">How can patients and providers navigate the commercial CGT landscape described in previous sections and be sure that products advertised or otherwise offered to them meet established standards of safety and effectiveness? CGT products must undergo a rigorous process of quality, safety and efficacy demonstration under the oversight of regulatory agencies authorized by law to evaluate and approve drugs, biologics and medical devices. Such agencies can be either national, as with organizations such as Health Canada and the FDA, or transnational, as in the case of the European Union's (EU's) European Medicines Agency (EMA) (<a id="crf0040" href="#tbl0002">Table 2</a>). National medicine agencies of each EU country are accountable for clinical trials, manufacturing laboratories or “Hospital Exemption” authorizations. In general, a considerable body of preclinical research that establishes biological mechanisms of action and demonstration of safety and potential efficacy in (small and/or large) animal models is required before a new CGT product can be tested in humans [<a id="crf0041" href="#bib0011" role="doc-biblioref" data-xml-rid="bib0011">11</a>,<a id="crf0042" href="#bib0012" role="doc-biblioref" data-xml-rid="bib0012">12</a>]. The latter process takes place through phased clinical trials and can be accelerated by specific mechanisms, such as the Regenerative Medicine Advanced Therapy designation in the United States <a id="crf0043" href="#bib0013" role="doc-biblioref" data-xml-rid="bib0013">[13]</a>, the PRIME designation in the EU <a id="crf0044" href="#bib0014" role="doc-biblioref" data-xml-rid="bib0014">[14]</a> and the SAKIGAKE designation in Japan <a id="crf0045" href="#bib0015" role="doc-biblioref" data-xml-rid="bib0015">[15]</a>.</div><div class="figure-wrap"><figure id="tbl0002" class="table" data-figureviewer-ignore="true"><div class="table-wrap"><table data-figureviewer-ignore="true"><thead><tr class="rowsep" data-xml-align="left" data-xml-valign="top"><th id="en0006">Regulatory agency</th><th id="en0007">Hyperlink</th></tr></thead><tbody><tr><td id="en0008">Australia: Therapeutic Goods Administration (TGA)</td><td id="en0009"><a id="interref0001" href="https://www.tga.gov.au/" target="_blank">https://www.tga.gov.au/</a></td></tr><tr><td id="en0010">Brazil: Agência Nacional de Vigilância Sanitária (Anvisa)</td><td id="en0011"><a id="interref0002" href="https://www.gov.br/anvisa/pt-br" target="_blank">https://www.gov.br/anvisa/pt-br</a></td></tr><tr><td id="en0012">Canada: Health Canada</td><td id="en0013"><a id="interref0003" href="https://www.canada.ca/en/health-canada.html" target="_blank">https://www.canada.ca/en/health-canada.html</a></td></tr><tr><td id="en0014">China: National Medical Products Administration (NMPA)</td><td id="en0015"><a id="interref0004" href="http://english.nmpa.gov.cn/" target="_blank">http://english.nmpa.gov.cn/</a></td></tr><tr><td id="en0016">European Union: European Medicines Agency (EMA)</td><td id="en0017"><a id="interref0005" href="https://www.ema.europa.eu/en" target="_blank">https://www.ema.europa.eu/en</a></td></tr><tr><td id="en0018">India: Central Drugs Standard Control Organisation</td><td id="en0019"><a id="interref0006" href="https://cdsco.gov.in/opencms/opencms/en/Home" target="_blank">https://cdsco.gov.in/opencms/opencms/en/Home</a></td></tr><tr><td id="en0020">Iran: Iran Food & Drug Administration</td><td id="en0021"><a id="interref0007" href="https://www.fda.gov.ir/en" target="_blank">https://www.fda.gov.ir/en</a></td></tr><tr><td id="en0022">Japan: Pharmaceuticals and Medical Devices Agency (PMDA)</td><td id="en0023"><a id="interref0008" href="https://www.pmda.go.jp/english/index.html" target="_blank">https://www.pmda.go.jp/english/index.html</a></td></tr><tr><td id="en0024">New Zealand: Medicines and Medical Devices Safety Authority (MEDSAFE)</td><td id="en0025"><a id="interref0009" href="https://www.medsafe.govt.nz/" target="_blank">https://www.medsafe.govt.nz/</a></td></tr><tr><td id="en0026">Singapore: Health Sciences Authority (HSA)</td><td id="en0027"><a id="interref0010" href="https://www.hsa.gov.sg/" target="_blank">https://www.hsa.gov.sg/</a></td></tr><tr><td id="en0028">South Korea: Ministry of Food and Drug Safety (MFDS)</td><td id="en0029"><a id="interref0011" href="https://www.mfds.go.kr/eng/index.do" target="_blank">https://www.mfds.go.kr/eng/index.do</a></td></tr><tr><td id="en0030">Switzerland: Swissmedic</td><td id="en0031"><a id="interref0012" href="https://www.swissmedic.ch/swissmedic/en/home.html" target="_blank">https://www.swissmedic.ch/swissmedic/en/home.html</a></td></tr><tr><td id="en0032">USA: Food & Drug Administration (FDA)</td><td id="en0033"><a id="interref0013" href="https://www.fda.gov/" target="_blank">https://www.fda.gov/</a></td></tr></tbody></table></div><figcaption><span class="heading">Table 2</span><div id="spara002" role="paragraph">Regulatory agencies and their jurisdictions.</div><div class="core-table-tools"><ul><li><a class="core-table-show-action" href="/action/showFullTableHTML?isHtml=true&tableId=tbl0002&pii=S1465-3249%2823%2900064-6" target="_blank">Open table in a new tab</a></li></ul></div></figcaption></figure></div><div id="para0031" role="paragraph">Once a CGT product has been shown to be safe and effective, it can receive marketing authorization by the respective regulatory agency <a id="crf0046" href="#bib0016" role="doc-biblioref" data-xml-rid="bib0016">[16]</a>. In some cases, products receive conditional approval for a finite period, and post-market surveillance is required as additional data are collected <a id="crf0047" href="#bib0017" role="doc-biblioref" data-xml-rid="bib0017">[17]</a>. After additional data are generated, such conditionally approved products can receive full marketing authorization if safety and efficacy support such a determination, or they can have their conditional approval status withdrawn if post-marketing data prompts concerns about the safety and/or efficacy of such products. Approved and proven CGT products, where benefits are determined to exceed risks, are also usually eligible for reimbursement by health insurance providers (private or public). As already noted, pay-to-participate studies that do not meet these criteria and are not eligible for reimbursement may be signs of concerning/unconventional clinical practice.</div><div id="para0032" role="paragraph">There are additional mechanisms that ensure the access of patients with unmet and/or serious medical needs to unapproved products under the supervision of medicines agencies, such as the US FDA “Expanded Access” program and the “Hospital Exemption” program available in some European countries [<a id="crf0048" href="#bib0018" role="doc-biblioref" data-xml-rid="bib0018">18</a>,<a id="crf0049" href="#bib0019" role="doc-biblioref" data-xml-rid="bib0019">19</a>]. Regulatory flexibility providing access to investigational products is important, as not all individuals who have reasonable grounds for seeking access to investigational products meet clinical trial inclusion criteria. However, regulatory exceptions are sometimes abused and need to be carefully monitored so that they do not become problematic loopholes. Therefore, such mechanisms need to be used judiciously and importantly remain under the oversight of regulatory agencies.</div><div id="para0033" role="paragraph">An unfortunate abundance of CGT products that are unproven and unapproved by regulatory agencies is offered worldwide for various conditions and diseases. Many of these products and their administration have been shown to result in adverse physical effects, from blindness to infections or even death, and considerable financial and psychological harm <a id="crf0050" href="#bib0020" role="doc-biblioref" data-xml-rid="bib0020">[20]</a>. These adverse outcomes clearly demonstrate the need for conducting appropriate clinical trials, ensuring through early safety testing that products with high-risk profiles do not enter the marketplace.</div><div id="para0034" role="paragraph">In contrast, approved and proven CGT products are marketed after their quality, safety and effectiveness have been demonstrated through carefully conducted and monitored clinical testing under oversight of regulatory agencies. Although approved CGTs are not totally free of risk, they must have a favorable benefit-to-risk ratio before they are approved. Furthermore, regulatory oversight makes possible their withdrawal from the marketplace should the additional data obtained post-marketing demonstrate that benefits of use do not outweigh risks.</div></section><section id="sec-4"><h2>Levels of Evidence Required for Widespread Approval</h2><div id="para0035" role="paragraph">Since current levels of scientific evidence do not justify or do not yet justify the commercial or clinical use of many CGT interventions, it is reasonable to ask what criteria should be applied before a product might be considered “proven” and sufficiently evidence-based for inclusion in current standard of medical care. The gold standard for any medicinal product to be considered “proven” is well-designed and sufficiently powered, strictly supervised, regulated, peer-reviewed, published clinical research studies. Preferably these studies are randomized in a double-blind fashion with a control arm using a placebo, sham surgical intervention or current standard of care. However, there are sometimes factors that prevent the attainment of gold standard randomized trials, such as in ultra-rare diseases that limit accrual of sufficient numbers of research participants and preclude randomization.</div><div id="para0036" role="paragraph">There are considerable risks involved if proper evidence of clinical benefit and safety are not proven by a structured and phased approach to clinical trial progression. If a medical product receives accelerated approval without evidence of effectiveness, then the likelihood of ever generating scientific evidence is greatly reduced. Sponsors and product developers would not be motivated to demonstrate effectiveness because they are already in the market and often have no direct competition. Patients and their family members do not wish to miss any chance that a therapy might offer a benefit, especially if the risks or harm are perceived as low. Subsequent efforts to conduct randomized controlled trials are therefore likely to experience significant difficulties recruiting study participants. Social media and internet-based communications often exacerbate the ambiguity perceived between “proven” and “unproven” therapies in patient communities. Regulators may be unable to challenge political lobbying, advocacy and market forces.</div><div id="para0037" role="paragraph">It should also be recognized that economic interests and nationalism may spur regional variances in regulatory standards <a id="crf0051" href="#bib0021" role="doc-biblioref" data-xml-rid="bib0021">[21]</a>. These national differences in standards and oversight structures can lead to regulatory arbitrage, in which parties attempting to distribute and sell unproven CGT products cluster in jurisdictions with lax regulatory standards or ineffective law enforcement mechanisms. If the metaphorical horse has bolted from the barn and approval is granted before at least one pivotal trial is completed, then possibly effective medicinal products may languish in a perpetual state of uncertainty.</div></section><section id="sec-5"><h2>Reporting Mechanisms in the United States and Worldwide</h2><div id="para0038" role="paragraph">Multiple factors drive practitioners to create businesses that offer medical services (which can be lucrative) using biological materials that have not been adequately tested for safety and/or efficacy. Once treated, patients who experience negative consequences, such as side effects, infections or other harms, risk having little recourse against such clinicians <a id="crf0052" href="#bib0022" role="doc-biblioref" data-xml-rid="bib0022 bib0023 bib0024">[22–24]</a>. Complications may also not be recognized by the patients as resulting from the treatment received. Litigation can be costly, and protracted, with no assurance of a favorable outcome for plaintiffs. Patients who believe they have been harmed as a result of being administered such products can encounter difficulties finding legal representation if settlements of any kind are likely to be modest due to caps on medical malpractice verdicts or other constraints. Furthermore, some businesses and clinicians are inadequately insured, and there is little prospect of plaintiffs recovering their funds. Furthermore, patients with serious health problems often are in a poor position to participate in what can be years of costly, stressful and demanding litigation, all of which can unfold while patients suffer and their health declines <a id="crf0054" href="#bib0025" role="doc-biblioref" data-xml-rid="bib0025">[25]</a>. Patients may self-censor reporting adverse events or lack of response from an intervention that they have paid for out-of-pocket. Where can a patient go when they believe they have been harmed by an unproven CGT product, suffered financial losses with no clinical benefits or otherwise conclude they suffered harm of some kind <a id="crf0055" href="#bib0026" role="doc-biblioref" data-xml-rid="bib0026">[26]</a>?</div><div id="para0039" role="paragraph">Unproven CGT products as well as various autologous tissues and other products, such as primary human cells and exosomes, that are not manufactured for use in humans are reasonably easy to access. For a practitioner who sells unlicensed and unproven cell-based interventions, obtaining such products is a straightforward process. For example, many products can be purchased online, from both reputable and suspect sources, marked up in price, and then sold to patients at a considerable profit. Similarly, medical devices may be repurposed for non-authorized CGT-related uses through relatively minor changes in the operating procedures. From there, and using local personnel, the practitioner can manufacture unlicensed and unproven CGT products on the premises. These products and devices as well as other scientific and medical equipment can be used to suggest the legitimacy of the practitioner's office. It is also not uncommon for a clinic or business to have had inspection of the devices by a regulatory agency and use this to further legitimize use of the devices in unproven CGT offerings. For example, having a centrifuge inspected and validated for operation does not confer or imply approval for use in unproven or unauthorized CGTs. In parallel with suggestion of “legitimacy” of the physical space in the clinic, patients/consumers may further be attracted to displays and videos of patient testimonials <a id="crf0056" href="#bib0027" role="doc-biblioref" data-xml-rid="bib0027 bib0028 bib0029">[27–29]</a>. Although some states in the United States and regions of the EU may have requirements that businesses post displays stating that the procedures being provided are not approved by regulatory agencies, the majority of the world has no such requirements.</div><div id="para0040" role="paragraph">One mechanism that would seem to alleviate ambiguity in the use of unproven CGTs would be obtaining consent from patients before treatment. In a research setting, such consent includes a discussion of the procedures, the risks, the benefits, the alternatives and the costs of the intervention. The content of informed consent documents is codified in numerous regulations worldwide, notably the International Conference on Harmonization Good Clinical Practice Guideline <a id="crf0058" href="#bib0030" role="doc-biblioref" data-xml-rid="bib0030">[30]</a>. Review of the product-specific or research procedure-specific details as described in the informed consent form is conducted by an ethics committee or institutional review board. Unfortunately, informed consent is not always obtained for unproven CGTs and, when it is, review by an ethics committee or institutional review board is not always guaranteed. Written consent documents may not be provided to the recipients of unproven CGTs and, as noted, the use of misrepresentations is rampant in unproven CGTs.</div><div id="para0041" role="paragraph">The sheer volume of direct-to-consumer businesses offering unproven CGTs and the exploitation of regulatory ambiguity and/or loopholes have resulted in a global marketplace with widespread patient exploitation. Further reasons exacerbating this problem are the inability of understaffed regulatory agencies to perform rigorous and extensive inspections of such businesses and take enforcement actions, the absence of global regulatory convergence and transnational travel (also known as medical tourism) of patients seeking unproven CGTs.</div><section id="sec-5-1"><h3>Recourse/reporting of unproven CGTs and questionable practitioners</h3><div id="para0042" role="paragraph">Countries with developed regulatory frameworks for approving CGTs often have product safety reporting systems that consumers, patients and clinicians can use. These systems often reside within the product approval framework under country-specific drug approval agencies. Such systems are intended to capture adverse safety events that appear to result from the use of a therapeutic product intended to confer medical benefit to the recipient. These reporting systems can also be used to report unintended events observed with unproven CGT products.</div><div id="para0043" role="paragraph">Examples of such reporting pathways include the following:<div id="celist0202" role="list"><div id="celistitem0010" role="listitem"><div class="label">a)</div><div class="content"><div id="para0044" role="paragraph">The US FDA has a program called MedWatch that captures and analyzes potential adverse events and product complaints <a id="crf0059" href="#bib0031" role="doc-biblioref" data-xml-rid="bib0031">[31]</a>. For serious adverse events occurring while a product is being studied under an Investigational New Drug Application, reporting to the FDA is mandatory. Reporting serious adverse events to the FDA outside of an Investigational New Drug Application is voluntary. Such voluntary reporting can be done by the patient or a health care professional. In plain language, the FDA encourages anyone who has been “hurt or had a bad side effect following treatment with anything that was supposed to be a regenerative medicine product, including, for example stem cell products and exosome products” to report such events to them. The form used for reporting serious adverse events, also referred to as FDA form 3500, is online and includes clear guidance regarding how it should be completed. The voluntary reporting form provides room for the patient or their health care provider to describe the event and the outcome of the event, the suspected product, health information about the patient and contact information for the individual reporting the event (although the reporting individual can ask for such information to not be shared with the manufacturer). The FDA uses these reports for safety surveillance. Patients, consumers and health care providers can stay informed of ongoing MedWatch activities by subscribing to one or more electronic distribution tools. The US Federal Trade Commission (FTC) works with FDA as needed to bring legal proceedings against providers who engage in deceptive advertising. The FTC files a complaint when it has “reason to believe” that the law has been or is being violated and it appears to the Commission that a proceeding is in the public interest. Stipulated final injunctions/orders have the force of law when approved and signed by the District Court judge. The FTC has been particularly active during the pandemic, focusing on businesses selling unproven and unlicensed stem cell products and other interventions as purported treatments, “immune boosters,” or preventive measures for coronavirus disease 2019 <a id="crf0060" href="#bib0032" role="doc-biblioref" data-xml-rid="bib0032">[32]</a>. Consumer complaints can be filed online. American Medical Association members are bound by a code of medical ethics to act professionally [<a id="crf0061" href="#bib0033" role="doc-biblioref" data-xml-rid="bib0033">33</a>,<a id="crf0062" href="#bib0034" role="doc-biblioref" data-xml-rid="bib0034">34</a>], but the American Medical Association does not have the legal authority or possess the proper resources to investigate individual cases and complaints. Therefore, practitioners are principally subject to oversight at the level of their state medical licensing boards.</div></div></div><div id="celistitem0012" role="listitem"><div class="label">b)</div><div class="content"><div id="para0046" role="paragraph">The EMA has issued public warnings about using unproven cell therapies that may be unsafe or ineffective <a id="crf0063" href="#bib0027" role="doc-biblioref" data-xml-rid="bib0027">[27]</a>. Physicians, institutions, companies or individuals who have questions about the regulatory status and/or proven safety and efficacy characteristics of a product are encouraged to contact the EMA or their National Competent Authority. EMA-reported Safety Adverse Event information is disclosed through language/country-specific databases. The centralized European database, EudraVigilance, is obligatory for marketing authorization holders and sponsors of clinical trials and since June 2022 it is mandatory to report side effects.</div></div></div><div id="celistitem0013" role="listitem"><div class="label">c)</div><div class="content"><div id="para0047" role="paragraph">Health Canada has issued public notice of the risks associated with using unproven CGTs <a id="crf0064" href="#bib0035" role="doc-biblioref" data-xml-rid="bib0035">[35]</a>. A position paper by Health Canada <a id="crf0065" href="#bib0036" role="doc-biblioref" data-xml-rid="bib0036">[36]</a> on autologous cell therapy products notes the legal distinctions between the Canadian regulatory framework and the EMA regulatory framework. However, on a practical level, there is shared emphasis in warning against the risks posed by unproven CGT use. Health Canada provides a consumer reporting portal for reporting product complaints, as well as the ability to specifically report Adverse Events by a variety of means. In addition, consumer complaints can be filed to Canada's Competition Bureau.</div></div></div><div id="celistitem0014" role="listitem"><div class="label">d)</div><div class="content"><div id="para0048" role="paragraph">Australia's Therapeutic Goods Administration uses reporting portals for practitioners and patients similar to those previously described. In particular, the Agency clearly encourages consumers to report advertising that may be false, misleading or deceptive. New Zealand's Commerce Commission allows for registering complaints regarding false and misleading behavior, of which offering unlawful therapies or making unfounded marketing claims for unproven CGTs would be representative examples.</div></div></div><div id="celistitem0015" role="listitem"><div class="label">e)</div><div class="content"><div id="para0049" role="paragraph">Asia has regulatory agencies of multiple jurisdictions actively engaging with the regenerative medicine industry. Japan's Pharmaceuticals and Medical Devices Agency is responsible for pharmacovigilance activities including both pre-marketing safety reporting as well as post-market vigilance. Japan has a separate consumer protection government organization that spans all consumer impact areas. Likewise, Korea has a system called KAERS (Korea Adverse Event Reporting System) that facilitates reporting and management of adverse event reports.</div></div></div><div id="celistitem0016" role="listitem"><div class="label">f)</div><div class="content"><div id="para0050" role="paragraph">In South and Central America, there are also examples of systems developed to capture reports of adverse events in patients, inclusive of licensed and unlicensed products. In Brazil, such data can be reported in a system known as VigiMed. Argentina has an online form that also allows for reporting of such events.</div></div></div></div></div><div id="para0051" role="paragraph">See <a id="crf0066" href="#tbl0003">Table 3</a> for more information and the related web links on reporting pathways.</div><div class="figure-wrap"><figure id="tbl0003" class="table" data-figureviewer-ignore="true"><div class="table-wrap"><table data-figureviewer-ignore="true"><thead><tr class="rowsep" data-xml-align="left" data-xml-valign="top"><th id="en0034">Country or jurisdiction</th><th id="en0035">Regulatory or professional body</th><th id="en0036">Hyperlink</th></tr></thead><tbody><tr><td id="en0037">Argentina</td><td id="en0038">Administración Nacional de Medicamentos, Alimentos y Tecnología Médica (ANMAT)</td><td id="en0039"><a id="interref0014" href="https://www.argentina.gob.ar/sites/default/files/farmacovigilancia-ficha-eventos-adversos-pacientes.pdf" target="_blank">https://www.argentina.gob.ar/sites/default/files/farmacovigilancia-ficha-eventos-adversos-pacientes.pdf</a></td></tr><tr><td id="en0040">Australia</td><td id="en0041">Therapeutic Goods Administration (TGA)</td><td id="en0042"><a id="interref0015" href="https://www.tga.gov.au/safety-information" target="_blank">https://www.tga.gov.au/safety-information</a><br /><a id="interref0016" href="https://www.tga.gov.au/news/news/stem-cell-treatments-and-regulation-quick-guide-consumers" target="_blank">https://www.tga.gov.au/news/news/stem-cell-treatments-and-regulation-quick-guide-consumers</a><br /><a id="interref0017" href="https://www.tga.gov.au/complying-advertising-requirements" target="_blank">https://www.tga.gov.au/complying-advertising-requirements</a><br /><a id="interref0018" href="https://www.tga.gov.au/advertising-enforcement-and-outcomes" target="_blank">https://www.tga.gov.au/advertising-enforcement-and-outcomes</a></td></tr><tr><td id="en0043">Belgium</td><td id="en0044">Federal Agency for Medicines and Health Products (FAMHP)</td><td id="en0045"><a id="interref0019" href="https://www.famhp.be/en" target="_blank">https://www.famhp.be/en</a></td></tr><tr><td id="en0046">Brazil</td><td id="en0047">Agência Nacional de Vigilância Sanitária (Anvisa)</td><td id="en0048"><a id="interref0020" href="https://primaryreporting.who-umc.org/BR" target="_blank">https://primaryreporting.who-umc.org/BR</a></td></tr><tr><td id="en0049">Canada</td><td id="en0050">Health Canada</td><td id="en0051"><a id="interref0021" href="https://healthycanadians.gc.ca/apps/radar/MD-IM-0005.08.html" target="_blank">https://healthycanadians.gc.ca/apps/radar/MD-IM-0005.08.html</a><br /><a id="interref0022" href="https://www.competitionbureau.gc.ca/eic/site/cb-bc.nsf/frm-eng/GH%c3%89T-7TDNA5" target="_blank">https://www.competitionbureau.gc.ca/eic/site/cb-bc.nsf/frm-eng/GH%c3%89T-7TDNA5</a><br /><a id="interref0023" href="https://www.canada.ca/en/health-canada/services/drugs-health-products/medeffect-canada/adverse-reaction-reporting.html" target="_blank">https://www.canada.ca/en/health-canada/services/drugs-health-products/medeffect-canada/adverse-reaction-reporting.html</a></td></tr><tr><td id="en0052">EU</td><td id="en0053">European Medicines Agency</td><td id="en0054"><a id="interref0024" href="https://www.ema.europa.eu/en/human-regulatory/research-development/pharmacovigilance/eudravigilance/access-eudravigilance-data" target="_blank">https://www.ema.europa.eu/en/human-regulatory/research-development/pharmacovigilance/eudravigilance/access-eudravigilance-data</a><br /><a id="interref0025" href="https://www.adrreports.eu/" target="_blank">https://www.adrreports.eu/</a></td></tr><tr><td id="en0055">France</td><td id="en0056">Agence nationale de sécurité du médicament et des produits de santé (ANSM)</td><td id="en0057"><a id="interref0026" href="https://ansm.sante.fr/documents/reference/declarer-un-effet-indesirable" target="_blank">https://ansm.sante.fr/documents/reference/declarer-un-effet-indesirable</a></td></tr><tr><td id="en0058">Japan</td><td id="en0059">Consumer Affairs Agency</td><td id="en0060"><a id="interref0027" href="https://www.caa.go.jp/en/law/" target="_blank">https://www.caa.go.jp/en/law/</a></td></tr><tr><td id="en0061">New Zealand</td><td id="en0062">Commerce Commission</td><td id="en0063"><a id="interref0028" href="https://comcom.govt.nz/make-a-complaint" target="_blank">https://comcom.govt.nz/make-a-complaint</a></td></tr><tr><td id="en0064">South Korea</td><td id="en0065">Korea Institute of Drug Safety & Risk Management (KIDS)</td><td id="en0066"><a id="interref0029" href="https://www.drugsafe.or.kr/iwt/ds/en/report/WhatIsKAERS.do" target="_blank">https://www.drugsafe.or.kr/iwt/ds/en/report/WhatIsKAERS.do</a></td></tr><tr><td id="en0067">USA</td><td id="en0068">Federal Trade Commission</td><td id="en0069"><a id="interref0030" href="https://reportfraud.ftc.gov/#/" target="_blank">https://reportfraud.ftc.gov/#/</a></td></tr><tr><td id="en0070">USA</td><td id="en0071">Food and Drug Administration (MedWatch Program)</td><td id="en0072"><a id="interref0031" href="https://www.fda.gov/safety/medwatch-fda-safety-information-and-adverse-event-reporting-program" target="_blank">https://www.fda.gov/safety/medwatch-fda-safety-information-and-adverse-event-reporting-program</a></td></tr><tr><td id="en0073">USA</td><td id="en0074">Federation of State Medical Boards (FSMB)</td><td id="en0075"><a id="interref0032" href="https://www.fsmb.org/contact-a-state-medical-board" target="_blank">https://www.fsmb.org/contact-a-state-medical-board</a></td></tr></tbody></table></div><figcaption><span class="heading">Table 3</span><div id="spara003" role="paragraph">Adverse event reporting mechanisms and databases worldwide.</div><div class="core-table-tools"><ul><li><a class="core-table-show-action" href="/action/showFullTableHTML?isHtml=true&tableId=tbl0003&pii=S1465-3249%2823%2900064-6" target="_blank">Open table in a new tab</a></li></ul></div></figcaption></figure></div><div id="para0052" role="paragraph">Overall, some countries have well-defined, accessible and easy-to-use mechanisms for patients/consumers to file complaints and adverse events. However, not all jurisdictions provide such reporting mechanisms. Even within countries that have developed regulatory frameworks, reporting may be limited to health care professionals and industry (and enforcement is not guaranteed to follow reported complaints). Even more concerning, many low- and middle-income countries have minimal or no regulations regarding medicinal products. When considering unproven CGT products, these gaps become even more concerning. Many regions would benefit from better-defined and more effective reporting mechanisms inclusive of patient-reported adverse events. This reporting would facilitate collection of data on adverse effects resulting from administration of unproven and unlicensed CGTs and may also increase the likelihood of more effective regulatory responses to agents and facilities selling and administering such products. In parallel, a push toward global, coordinated efforts to curb the growth of the direct-to-consumer industry offering unproven CGTs is gaining traction. The World Health Organization has already issued a white paper proposing a global risk-based system for evaluation of CGT products and regulatory convergence that includes increasing collaboration between regulatory agencies from high income and low- and middle-income countries <a id="crf0067" href="#bib0037" role="doc-biblioref" data-xml-rid="bib0037">[37]</a>. In this context, the proposal for a World Health Organization Expert Advisory Committee on Regenerative Medicine <a id="crf0068" href="#bib0038" role="doc-biblioref" data-xml-rid="bib0038">[38]</a> is timely and puts emphasis on existing international health policy bodies to effect change and provide guidance.</div><div id="para0053" role="paragraph">Clinical research and development are a continuum. Complex biological products are created first from an idea or hypothesis based on understood biological mechanisms of action. The research that follows bears out the hypothesis or fails to support it and/or branches off into related treatment areas. This is a costly, often non-linear and time-consuming process of incremental investigations before treating any patient. The return on investment or approved, commercially available treatment timelines are typically many years. By contrast, unproven CGT providers, aided by low-cost barriers to entry, prey on patients who believe they have exhausted all credible options. Although costs for unproven cell and gene interventions can vary widely, patients frequently endure considerable financial strain, as witnessed by the increase in crowdfunding campaigns for such interventions and patient reports of substantial financial losses without evident improvement in their condition [<a id="crf0069" href="#bib0026" role="doc-biblioref" data-xml-rid="bib0026">26</a>,<a id="crf0070" href="#bib0039" role="doc-biblioref" data-xml-rid="bib0039">39</a>]. Patient options for redress are limited to what they can economically afford and have the knowledge, persistence and time to pursue. The financial burden can be particularly onerous for the most vulnerable patients, such as low-income individuals or individuals with limited access to vetted medical information and health care. Deployment of savvy marketing techniques by direct-to-consumer businesses affect disproportionally such individuals and may lead to a downward spiral of accumulating financial debt and physical and psychological harms [<a id="crf0071" href="#bib0040" role="doc-biblioref" data-xml-rid="bib0040">40</a>,<a id="crf0072" href="#bib0041" role="doc-biblioref" data-xml-rid="bib0041">41</a>]. Importantly, many patients, families, and caregivers are unaware of the reporting mechanisms described previously and in <a id="crf0073" href="#tbl0003">Table 3</a>. Patients (and patient families) therefore need assurance before committing that any treatment being considered as well as relevant alternatives have been thoroughly reviewed by legally recognized regulatory authorities. As shown in <a id="crf0074" href="#box1">Box 1</a>, there are steps that patients and caregivers can take if they believe one has been harmed by administration of unproven cell- or gene-based interventions.</div><div id="para0054" role="paragraph">Local and national agencies in many countries are acting to warn, investigate and take action against businesses selling unproven CGTs <a id="crf0075" href="#bib0042" role="doc-biblioref" data-xml-rid="bib0042">[42]</a>. However, often they are resource-constrained and only able to effectively respond when they have broad knowledge and insight. Patients can assist such bodies in launching investigations by filing detailed reports when there is reason to believe they have been harmed as a result of receiving an unproven CGT ([<a id="optagVRaZCK6L" href="#bib0022" role="doc-biblioref" data-xml-rid="bib0022 bib0025">22,25</a>] and <a id="crf0076" href="#tbl0003">Table 3</a><b>)</b>.</div></section></section><section id="sec-6"><h2>Actions ISCT Members Can Take to Address Direct-to-Consumer Marketing of Unproven CGTs</h2><div id="para0055" role="paragraph">Government agencies such as the US FDA, the EMA and their regional equivalents across the globe are ultimately responsible for determining when a CGT is considered “proven” to be safe and effective or where the potential benefits outweigh the risks. However, we can all play a role in reinforcing the need for rigorous evaluation and helping consumers avoid harm <a id="crf0077" href="#bib0034" role="doc-biblioref" data-xml-rid="bib0034">[34]</a>, from products that have entered the marketplace without being subjected to such careful and independent assessment. Physicians can be particularly effective in addressing the direct-to-consumer marketing of unproven CGT products as they discuss treatment options with their patients. Oftentimes physicians are unprepared to address patient questions related to CGTs due to a lack of education regarding novel cell-based treatments and their experimental status. Regrettably, clinical practitioners can themselves became purveyors of unproven CGTs, frequently outside their scope of training <a id="crf0078" href="#bib0043" role="doc-biblioref" data-xml-rid="bib0043">[43]</a> and sometimes with dire consequences, as research in Canada <a id="crf0079" href="#bib0044" role="doc-biblioref" data-xml-rid="bib0044">[44]</a>, the United States <a id="crf0080" href="#bib0045" role="doc-biblioref" data-xml-rid="bib0045">[45]</a> and Australia <a id="crf0081" href="#bib0023" role="doc-biblioref" data-xml-rid="bib0023">[23]</a> has shown.</div><div id="para0056" role="paragraph">Here are some simple ways ISCT members can make a difference whether they are researchers, CGT developers in industry, clinical practitioners or quality professionals:<div id="celist0005" role="list"><div id="celistitem0017" role="listitem"><div class="label">-</div><div class="content"><div id="para0057" role="paragraph">Take care when you communicate your science: Ensure that you do not add to community misunderstanding about the availability of CGTs. When discussing your workࣧ -or advances in the fieldࣧ- with journalists, the public or in social media, stick to claims that are evidence-based and avoid engaging in hyperbole <a id="crf0082" href="#bib0046" role="doc-biblioref" data-xml-rid="bib0046">[46]</a>. Carefully review any announcements prepared and promoted by your institution, university or company to ensure that the communication strikes the right balance between sharing your enthusiasm for your work and outlining the steps that will be required before the intervention may be available to patients. Where you are involved in conducting clinical research, be prepared to publish and discuss the outcomes, and their implications, no matter whether the findings are encouraging, discouraging or ambiguous <a id="crf0083" href="#bib0047" role="doc-biblioref" data-xml-rid="bib0047">[47]</a>.</div></div></div><div id="celistitem0018" role="listitem"><div class="label">-</div><div class="content"><div id="para0058" role="paragraph">Correct misrepresentations about CGTs in the media: Where you see your work or that of colleagues misrepresented, make efforts to correct the reporting. Journalists are as interested in getting the story right as you are, so get in touch. In the unlikely event that they fail to respond, contact professional bodies that oversee journalism and report your concerns.</div></div></div><div id="celistitem0019" role="listitem"><div class="label">-</div><div class="content"><div id="para0059" role="paragraph">Report concerning practices: Take a stance if you come across clinics or companies making therapeutic claims that cannot be scientifically substantiated. Report your concerns about coverage online, in mainstream or social media or through other forms of advertising to the relevant regulatory body. This includes those charged with oversight of manufacturing and provision of therapeutic products as well as agencies who oversee standards in health care or the practice of medicine, such as US state medical boards and Canada's provincial Colleges of Physicians and Surgeons. There is usually a simple online form on which you can report questionable practices, such as the provision of unapproved therapeutic products. (See also “Reporting mechanisms in the US and worldwide” in <a id="crf0084" href="#tbl0003">Table 3</a> of this guide.)</div></div></div><div id="celistitem0020" role="listitem"><div class="label">-</div><div class="content"><div id="para0060" role="paragraph">Contact the ISCT Committee on the Ethics of Cell and Gene Therapy and/or relevant professional society or association in your region and alert them to what you have seen. They may know of research groups or agencies who monitor the advertising and provision of unproven therapies in your jurisdiction and your report will provide valuable insight into contemporary practices.</div><div id="para0061" role="paragraph">This advice is not just relevant to those involved in laboratory and clinical research but also to manufacturers and suppliers who may be alerted to irregular practices through product, equipment and reagent requests coming from clinics and health care providers involved in the sale and administration of unproven CGTs.</div></div></div><div id="celistitem0022" role="listitem"><div class="label">-</div><div class="content"><div id="para0062" role="paragraph">Partner with patient advocacy groups and support services: Reach out to groups in your community that share an interest in a particular condition or application. Offer to speak or write about your work. This can be a meaningful way to enhance community understanding about current research and clinical applications in CGTs and to warn about practices that may be bypassing clinical evaluation and regulatory approval. It is also an effective way to meet people in your community and learn more about the condition in which you are interestedࣧ -particularly for graduate researchers and students.</div></div></div><div id="celistitem0023a" role="listitem"><div class="label">-</div><div class="content"><div id="para0063" role="paragraph">Respond to those asking for help: You have probably already been asked by a stranger or maybe even a relative or a friend for advice about whether CGTs or regenerative medicine could help them or their loved one. Carefully listen to their inquiry and then provide them with links to reputable sources of online information, such as the ISCT, the International Society for Stem Cell Research and regional initiatives such as CIRM, EuroStemCell and Stem Cells Australia (<a id="crf0085" href="#tbl0004">Table 4</a>). You could also encourage the person making the enquiry to contact an appropriate patient foundation or advocacy or support group. Finally, and importantly, encourage them to talk to their medical specialist or family physician, rather than the doctor or clinic trying to sell them a simple solution, about their health care options.</div><div class="figure-wrap"><figure id="tbl0004" class="table" data-figureviewer-ignore="true"><div class="table-wrap"><table data-figureviewer-ignore="true"><thead><tr class="rowsep" data-xml-align="left" data-xml-valign="top"><th id="en0076">Source of information</th><th id="en0077">Resource name and hyperlink</th><th id="en0078">Notes</th></tr></thead><tbody><tr><td id="en0079">International Society for Cell & Gene Therapy (ISCT)</td><td id="en0080"><a id="interref0037z1" href="https://www.isct-unprovencellulartherapies.org/patient-resources/" target="_blank">ISCT Committee on the Ethics of Cell and Gene Therapy</a></td><td id="en0081">Includes the ISCT Reference Guide on Unproven Cell-Based Interventions, the ISCT Guide of Cell/Gene Products with Marketing Authorization and a COVID-19 Research Spotlight</td></tr><tr><td id="en0082">International Society for Stem Cell Research (ISSCR)</td><td id="en0083"><a id="interref0037z2" href="https://www.closerlookatstemcells.org/" target="_blank">Closer Look at Stem Cells</a></td><td id="en0084">Includes the “Patient Handbook on Stem Cell Therapies” and disease-specific Fact Sheets</td></tr><tr><td id="en0085">Stem Cells Australia</td><td id="en0086"><a id="interref0037z3" href="https://stemcellsaustralia.edu.au/" target="_blank">Stem Cells Australia</a></td><td id="en0087">Includes Q&A on stem cell treatments and information on the status of cell-based treatments for a wide variety of diseases/conditions</td></tr><tr><td id="en0088">EuroStemCell (a European network of scientists and academics)</td><td id="en0089"><a id="interref0037z4" href="https://www.eurostemcell.org/" target="_blank">EuroStemCell</a></td><td id="en0090">Includes information on various stem cell types, diseases/conditions, and educational videos</td></tr><tr><td id="en0091">German Stem Cell Network</td><td id="en0092"><a id="interref0037z5" href="https://de.gscn.org/Portals/0/Dokumente/AnnualReport/Einzelartikel2017/GSCN-Report_2017-18_EN_unproven.pdf?ver=2019-01-09-143904-573" target="_blank">Unproven Stem Cell Therapies</a></td><td id="en0093"> </td></tr><tr><td id="en0094">CIRM (California Stem Cell Agency)</td><td id="en0095"><a id="interref0037z6" href="https://www.cirm.ca.gov/patients" target="_blank">CIRM Patient Resources</a></td><td id="en0096">Includes information on CIRM-funded clinical trials, disease research programs, and patient stories</td></tr><tr><td id="en0097">Stem Cell Network (Canada)</td><td id="en0098"><a id="interref0037z8j" href="https://stemcellnetwork.ca/stem-cells/" target="_blank">Stem Cells</a></td><td id="en0099">Includes educational videos and profiles of stem cell researchers</td></tr><tr><td id="en0100">American Society of Gene+Cell Therapy (ASGCT)</td><td id="en0101"><a id="interref0037a8a" href="https://patienteducation.asgct.org/" target="_blank">Gene & Cell Therapy Education</a></td><td id="en0102"> </td></tr><tr><td id="en0103">European Society of Gene & Cell Therapy</td><td id="en0104"><a id="interref0037a2b" href="https://www.esgct.eu/gct-101" target="_blank">Gene & cell therapy 101</a></td><td id="en0105"> </td></tr><tr><td id="en0106">Children's Medical Research Institute-Australia</td><td id="en0107"><a id="interref0037a2a" href="https://www.cmrijeansforgenes.org.au/research/research-explained/what-is-gene-therapy" target="_blank">What is Gene Therapy?</a></td><td id="en0108"> </td></tr><tr><td id="en0109" rowspan="4">US Food & Drug Administration (FDA)</td><td id="en0110"><a id="interref0037a2" href="https://www.fda.gov/vaccines-blood-biologics/enforcement-actions-cber/bimoteam-biologicsinternet-surveillanceother" target="_blank">CBER Untitled Letters</a></td><td id="en0111"> </td></tr><tr><td id="en0113"><a id="interref0037ae6" href="https://www.fda.gov/consumers/consumer-updates/how-gene-therapy-can-cure-or-treat-diseases" target="_blank">What Is Gene Therapy?</a></td><td id="en0114"> </td></tr><tr><td id="en0116"><a id="interref0037ae5" href="https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/approved-cellular-and-gene-therapy-products" target="_blank">Approved Cellular and Gene Therapy Products</a></td><td id="en0117"> </td></tr><tr><td id="en0119"><a id="interref0037ae4" href="https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/resources-related-regenerative-medicine-therapies" target="_blank">Resources Related to Regenerative Medicine Therapies</a></td><td id="en0120"> </td></tr><tr><td id="en0121">Consumer Reports</td><td id="en0122"><a id="interref0037ae3" href="https://www.consumerreports.org/medical-treatments-procedures/trouble-with-stem-cell-therapy/" target="_blank">The Trouble With Stem Cell Therapy</a></td><td id="en0123"> </td></tr><tr><td id="en0124">ProPublica</td><td id="en0125"><a id="interref0037ae2" href="https://www.propublica.org/article/amniotic-stem-cell-treatment-transplant-therapy" target="_blank">The Birth-Tissue Profiteers</a></td><td id="en0126"> </td></tr><tr><td id="en0127">Paul Knoepfler's lab</td><td id="en0128"><a id="interref0037ae1" href="https://ipscell.com/scope-global-stem-cell-outreach-program-for-education/" target="_blank">Stem Cell Outreach Program for Education</a></td><td id="en0129"> </td></tr></tbody></table></div><figcaption><div class="caption"><span class="heading">Table 4</span><div id="spara004" role="paragraph">Resources related to proven and unproven CGTs.</div></div><div class="notes"><div id="spara005" role="paragraph">CGT, cell-based, cell-derived and gene-based therapies/interventions; COVID-19, coronavirus disease 2019.</div></div><div class="core-table-tools"><ul><li><a class="core-table-show-action" href="/action/showFullTableHTML?isHtml=true&tableId=tbl0004&pii=S1465-3249%2823%2900064-6" target="_blank">Open table in a new tab</a></li></ul></div></figcaption></figure></div></div></div></div></div></section><section id="sec-7"><h2>Conclusions</h2><div id="para0064" role="paragraph">Businesses selling unlicensed and unproven stem cell interventions and related “regenerative medicine” products have now operated in the global marketplace for approximately two decades. ISCT has played an important role in drawing attention to problematic commercial and clinical activities that put patients at risk and expose them to unnecessary and foreseeable risks. ISCT has also been an engaged participant in broader public conversations about the importance of ensuring that safety and efficacy of CGTs are evaluated in well-designed and carefully conducted clinical trials that comply with all applicable ethical, legal, scientific, and clinical standards. This document reflects ISCT's commitment to promoting patient safety and public understanding by helping ISCT members, patients and other parties identify “red flags” associated with concerning practices and also understand the importance of conducting robust pre-clinical and clinical research to determine whether CGTs are backed by substantial safety and efficacy data and can justifiably be marketed for particular indications.</div></section><section id="sec-8"><h2>Author Contributions</h2><div id="para0065" role="paragraph">Conception and design of the study: BLL, LI. Acquisition of data: LI, NC, MF, BJG, ADL, MM, JEJR, LT, HRB, RC, FG, AS, DJW, PZ, BLL. Analysis and interpretation of data: LI, NC, MF, BJG, ADL, MM, JEJR, LT, HRB, RC, FG, AS, DJW, PZ, BLL. Drafting or revising the manuscript: LI, NC, MF, BJG, ADL, MM, JEJR, LT, HRB, RC, FG, AS, DJW, PZ, BLL. All authors have approved the final article.</div></section><section id="conflict" class="core-conflict"><h2>Declaration of Competing Interest</h2><div id="para0068" role="paragraph">Hamid R. Bidkhori is the chancellor of the Biomedical Research Ethics Committee of Academic Center for Education, Culture and Research (ACECR) - Mashhad. He is a member of the International Society for Cell & Gene Therapy (ISCT), the International Society for Extracellular Vesicles (ISEV) and the ISCT Committee on the Ethics of Cell and Gene Therapy. Rachele Ciccocioppo is a member of the Advisory Board of Takeda (Italy) for the use of mesenchymal stromal cells in fistulizing Crohn's disease. Natividad Cuende is a member of the Governing Council of the Agencia Española de Medicamentos y Productos Sanitarios (Spanish Medicine and Medical Device Agency). She is member of the ISCT Committee on the Ethics of Cell and Gene Therapy and the ISCT Legal and Regulatory Affairs Committee–Europe. She is also member of the Spanish Guarantee Committee for Donation and Use of Human Cells and Tissues of the Spanish Ministry of Science and Innovation. She is not paid for these roles. Bambi Grilley is affiliated with QBRegulatory Consulting LLC that has provided regulatory affairs and project management support to AlloVir, Marker Therapeutics, LOKON Pharma, Tessa Therapeutics and March Biosciences. She is a member of ISCT and its Ethics of Cell and Gene Therapy (ECGT) Committee and is the incoming Chief Regulatory Officer of ISCT. She is not paid for her roles in ISCT. Conflict of interest is managed in accordance with Baylor College of Medicine policy and oversight. Laertis Ikonomou has written an expert report in a class action lawsuit filed against a business selling unproven “stem cell”-based interventions, and wrote the report on a pro bono basis. He is a member of the ISCT and the International Society for Stem Cell Research (ISSCR) and the chair of the ISCT Committee on the Ethics of Cell and Gene Therapy. He is not paid for these roles. Conflict of interest is managed in accordance with University at Buffalo policy and oversight. Aaron D. Levine is a member of ISCT and its ECGT committee. He is not paid for these roles. Levine's research program is supported by the National Science Foundation (NSF) (Grant No. EEC-1648035). Bruce Levine has received compensation for serving on the scientific advisory boards of Akron Bio, Avectas, Immuneel, Immusoft, In8bio, Ori Biotech, Oxford Biomedica, UTC Therapeutics and Vycellix. He has received compensation for consulting for GSK. He has received compensation and equity from Capstan Therapeutics as a co-founder and member of the Scientific Advisory Board. As co-founder of Tmunity Therapeutics, he received equity. Conflict of interest is managed in accordance with University of Pennsylvania policy and oversight. Megan Munsie is a member of the International Society for Stem Cell Research and its Ethics Committee and Public Policy Committee. She is also the President of the Australasian Society for Stem Cell Research. Munsie's research program is supported by the Novo Nordisk Foundation Center for Stem Cell Medicine (NNF21CC0073729). John E. J. Rasko: employment: Royal Prince Alfred Hospital; consultancy and honoraria: Rarecyte, Gilead, Roche, Novartis, Bluebird Bio, Spark therapeutics, Cynata, Pfizer; equity: Genea; shareholder: Rarecyte, Woke; DSMB: Diamond Fanconi anemia trial; research funding: National Health and Medical Research Council (NHMRC), New South Wales Cancer Council, Cancer Institute NSW (CINSW), Therapeutic Innovation Australia, Philanthropic foundations; Chair, Gene Technology Technical Advisory Committee, Office of The Gene Technology Regulator, Australian Government. Leigh Turner served as a compensated expert witness for the US government in a criminal case and as a pro bono expert witness in a class action lawsuit. He is a member of ISCT and its ECGT committee. He is also a member of the International Society for Stem Cell Research and its Ethics Committee and Membership Committee. Turner's research program is supported by the Pew Charitable Trusts. Daniel J. Weiss served as a compensated expert witness for the US government in a criminal case and as a pro bono expert witness in a class action lawsuit. He is a member of ISCT and its ECGT committee and is former Chief Scientific Officer of the ISCT. He is not paid for his roles in the ISCT. Dr. Weiss has received compensation for consulting with Mesoblast Inc., NextCell Inc., United Therapeutics. Inc. and Vertex Inc. Conflict of interest is managed in accordance with University of Vermont policy and oversight. Patricia J. Zettler reports serving as a consultant to the US Food & Drug Administration. All the other authors have no commercial, proprietary, or financial interest in the products or companies described in this article.</div></section><section id="acknowledgments" role="doc-acknowledgments"><h2>Acknowledgments</h2><section id="sec-9"><h3>Acknowledgments</h3><div id="para0066" role="paragraph">The authors are grateful to the ISCT Head Office in Vancouver, Canada, for the kind support in developing and completing this article.</div></section><section id="sec-10"><h3>Funding</h3><div id="para0067" role="paragraph">No funding was received.</div></section></section></div></section><div class="core-linked-content"></div><section id="backmatter" data-extent="backmatter"><div class="core-container"><section id="references"><h2>References</h2><div id="bibliography" role="doc-bibliography"><div role="list"><div role="listitem" data-has="label"><div id="bib0001" class="citations"><div id="sbref0001" class="citation"><div class="citation-content"><div class="label">1.</div>ISCT Presidential Task Force on the Use of Unproven Cellular Therapies, Reference Guide, 2015. <a id="interref0033" href="https://www.isctglobal.org/about/isct-committees/ecgt/ptfreferenceguide" target="_blank">https://www.isctglobal.org/about/isct-committees/ecgt/ptfreferenceguide</a>. (Accessed March 3 2023).</div><div class="external-links"><div class="core-xlink-google-scholar"><a href="https://scholar.google.com/scholar?q=ISCT+Presidential+Task+Force+on+the+Use+of+Unproven+Cellular+Therapies%2C+Reference+Guide%2C+2015.+https%3A%2F%2Fwww.isctglobal.org%2Fabout%2Fisct-committees%2Fecgt%2Fptfreferenceguide.+%28Accessed+March+3+2023%29." target="_blank" aria-label="Open Google Scholar in new tab">Google Scholar</a></div></div></div></div></div><div role="listitem" data-has="label"><div id="bib0002" class="citations"><div id="sbref0002" class="citation"><div class="citation-content"><div class="label">2.</div><div>Cook, M. ∙ Richey, A. ∙ Brafman, D.A. ...</div><div><strong>Weighing up the evidence used by direct-to-consumer stem cell businesses</strong></div><em>Stem Cell Rep.</em> 2021; <strong>16</strong>:2852-2860</div><div class="external-links"><div class="core-xlink-fulltext"><a href="/servlet/linkout?suffix=e_1_5_1_2_2_2&dbid=4&doi=10.1016%2Fj.jcyt.2023.03.002&key=10.1016%2Fj.stemcr.2021.10.007&cf=fulltext&site=cell-site" target="_blank" aria-label="Open Full Text in new tab">Full Text</a></div><div class="core-xlink-pdf"><a href="/servlet/linkout?suffix=e_1_5_1_2_2_2&dbid=4&doi=10.1016%2Fj.jcyt.2023.03.002&key=10.1016%2Fj.stemcr.2021.10.007&cf=pdf&site=cell-site" target="_blank" aria-label="Open Full Text (PDF) in new tab">Full Text (PDF)</a></div><div class="core-xlink-pubmed"><a href="https://pubmed.ncbi.nlm.nih.gov/34767748/" target="_blank" aria-label="Open PubMed in new tab">PubMed</a></div><div class="core-xlink-google-scholar"><a href="https://scholar.google.com/scholar_lookup?doi=10.1016%2Fj.stemcr.2021.10.007&pmid=34767748" target="_blank" aria-label="Open Google Scholar in new tab">Google Scholar</a></div></div></div></div></div><div role="listitem" data-has="label"><div id="bib0003" class="citations"><div id="sbref0003" class="citation"><div class="citation-content"><div class="label">3.</div><div>Turner, L.</div><div><strong>ClinicalTrials.gov, stem cells and 'pay-to-participate' clinical studies</strong></div><em>Regen. Med.</em> 2017; <strong>12</strong>:705-719</div><div class="external-links"><div class="core-xlink-crossref"><a href="https://doi.org/10.2217/rme-2017-0015" target="_blank" aria-label="Open Crossref in new tab">Crossref</a></div><div class="core-xlink-scopus"><a href="/servlet/linkout?suffix=e_1_5_1_2_3_2&dbid=137438953472&doi=10.1016%2Fj.jcyt.2023.03.002&key=2-s2.0-85031315974" target="_blank" aria-label="Open Scopus in new tab">Scopus (51)</a></div><div class="core-xlink-pubmed"><a href="https://pubmed.ncbi.nlm.nih.gov/28721755/" target="_blank" aria-label="Open PubMed in new tab">PubMed</a></div><div class="core-xlink-google-scholar"><a href="https://scholar.google.com/scholar_lookup?doi=10.2217%2Frme-2017-0015&pmid=28721755" target="_blank" aria-label="Open Google Scholar in new tab">Google Scholar</a></div></div></div></div></div><div role="listitem" data-has="label"><div id="bib0004" class="citations"><div id="sbref0004" class="citation"><div class="citation-content"><div class="label">4.</div><div>Wagner, D.E. ∙ Turner, L. ∙ Panoskaltsis-Mortari, A. ...</div><div><strong>Co-opting of ClinicalTrials.gov by patient-funded studies</strong></div><em>Lancet Resp. Med.</em> 2018; <strong>6</strong>:579-581</div><div class="external-links"><div class="core-xlink-fulltext"><a href="/servlet/linkout?suffix=e_1_5_1_2_4_2&dbid=4&doi=10.1016%2Fj.jcyt.2023.03.002&key=10.1016%2FS2213-2600%2818%2930242-X&cf=fulltext&site=lancet-site" target="_blank" aria-label="Open Full Text in new tab">Full Text</a></div><div class="core-xlink-pdf"><a href="/servlet/linkout?suffix=e_1_5_1_2_4_2&dbid=4&doi=10.1016%2Fj.jcyt.2023.03.002&key=10.1016%2FS2213-2600%2818%2930242-X&cf=pdf&site=lancet-site" target="_blank" aria-label="Open Full Text (PDF) in new tab">Full Text (PDF)</a></div><div class="core-xlink-scopus"><a href="/servlet/linkout?suffix=e_1_5_1_2_4_2&dbid=137438953472&doi=10.1016%2Fj.jcyt.2023.03.002&key=2-s2.0-85048936852" target="_blank" aria-label="Open Scopus in new tab">Scopus (21)</a></div><div class="core-xlink-pubmed"><a href="https://pubmed.ncbi.nlm.nih.gov/29934051/" target="_blank" aria-label="Open PubMed in new tab">PubMed</a></div><div class="core-xlink-google-scholar"><a href="https://scholar.google.com/scholar_lookup?doi=10.1016%2FS2213-2600%2818%2930242-X&pmid=29934051" target="_blank" aria-label="Open Google Scholar in new tab">Google Scholar</a></div></div></div></div></div><div role="listitem" data-has="label"><div id="bib0005" class="citations"><div id="sbref0005" class="citation"><div class="citation-content"><div class="label">5.</div><div>Osborne, J. ∙ Pimentel, D.</div><div><strong>Science, misinformation, and the role of education</strong></div><em>Science.</em> 2022; <strong>378</strong>:246-248</div><div class="external-links"><div class="core-xlink-crossref"><a href="https://doi.org/10.1126/science.abq8093" target="_blank" aria-label="Open Crossref in new tab">Crossref</a></div><div class="core-xlink-scopus"><a href="/servlet/linkout?suffix=e_1_5_1_2_5_2&dbid=137438953472&doi=10.1016%2Fj.jcyt.2023.03.002&key=2-s2.0-85140282829" target="_blank" aria-label="Open Scopus in new tab">Scopus (31)</a></div><div class="core-xlink-pubmed"><a href="https://pubmed.ncbi.nlm.nih.gov/36264815/" target="_blank" aria-label="Open PubMed in new tab">PubMed</a></div><div class="core-xlink-google-scholar"><a href="https://scholar.google.com/scholar_lookup?doi=10.1126%2Fscience.abq8093&pmid=36264815" target="_blank" aria-label="Open Google Scholar in new tab">Google Scholar</a></div></div></div></div></div><div role="listitem" data-has="label"><div id="bib0006" class="citations"><div id="sbref0006" class="citation"><div class="citation-content"><div class="label">6.</div><div>Ikonomou, L. ∙ Levine, A.D. ∙ Hematti, P. ...</div><div><strong>Cell banking for cell and gene therapy-regulatory, ethical, and scientific considerations</strong></div><em>Bioprocess Int.</em> 2020; <strong>18</strong>, 20</div><div class="external-links"><div class="core-xlink-google-scholar"><a href="https://scholar.google.com/scholar?q=L.IkonomouA.D.LevineP.HemattiB.L.LevineCell+banking+for+cell+and+gene+therapy-regulatory%2C+ethical%2C+and+scientific+considerationsBioprocess+Int181-2%29i202020" target="_blank" aria-label="Open Google Scholar in new tab">Google Scholar</a></div></div></div></div></div><div role="listitem" data-has="label"><div id="bib0007" class="citations"><div id="sbref0007" class="citation"><div class="citation-content"><div class="label">7.</div><div>Srivastava, A. ∙ Mason, C. ∙ Wagena, E. ...</div><div><strong>Part 1: defining unproven cellular therapies</strong></div><em>Cytotherapy.</em> 2016; <strong>18</strong>:117-119</div><div class="external-links"><div class="core-xlink-fulltext"><a href="/servlet/linkout?suffix=e_1_5_1_2_7_2&dbid=4&doi=10.1016%2Fj.jcyt.2023.03.002&key=10.1016%2Fj.jcyt.2015.11.004&cf=fulltext&site=jcyt-site" target="_blank" aria-label="Open Full Text in new tab">Full Text</a></div><div class="core-xlink-pdf"><a href="/servlet/linkout?suffix=e_1_5_1_2_7_2&dbid=4&doi=10.1016%2Fj.jcyt.2023.03.002&key=10.1016%2Fj.jcyt.2015.11.004&cf=pdf&site=jcyt-site" target="_blank" aria-label="Open Full Text (PDF) in new tab">Full Text (PDF)</a></div><div class="core-xlink-pubmed"><a href="https://pubmed.ncbi.nlm.nih.gov/26719202/" target="_blank" aria-label="Open PubMed in new tab">PubMed</a></div><div class="core-xlink-google-scholar"><a href="https://scholar.google.com/scholar_lookup?doi=10.1016%2Fj.jcyt.2015.11.004&pmid=26719202" target="_blank" aria-label="Open Google Scholar in new tab">Google Scholar</a></div></div></div></div></div><div role="listitem" data-has="label"><div id="bib0008" class="citations"><div id="sbref0008" class="citation"><div class="citation-content"><div class="label">8.</div><div>Munsie, M. ∙ Lysaght, T. ∙ Hendl, T. ...</div><div><strong>Open for business: a comparative study of websites selling autologous stem cells in Australia and Japan</strong></div><em>Regen. Med.</em> 2017; <strong>12</strong>:777-790</div><div class="external-links"><div class="core-xlink-crossref"><a href="https://doi.org/10.2217/rme-2017-0070" target="_blank" aria-label="Open Crossref in new tab">Crossref</a></div><div class="core-xlink-scopus"><a href="/servlet/linkout?suffix=e_1_5_1_2_8_2&dbid=137438953472&doi=10.1016%2Fj.jcyt.2023.03.002&key=2-s2.0-85031320441" target="_blank" aria-label="Open Scopus in new tab">Scopus (35)</a></div><div class="core-xlink-pubmed"><a href="https://pubmed.ncbi.nlm.nih.gov/29125016/" target="_blank" aria-label="Open PubMed in new tab">PubMed</a></div><div class="core-xlink-google-scholar"><a href="https://scholar.google.com/scholar_lookup?doi=10.2217%2Frme-2017-0070&pmid=29125016" target="_blank" aria-label="Open Google Scholar in new tab">Google Scholar</a></div></div></div></div></div><div role="listitem" data-has="label"><div id="bib0009" class="citations"><div id="sbref0009" class="citation"><div class="citation-content"><div class="label">9.</div><div>Snyder, J. ∙ Turner, L.</div><div><strong>Selling stem cell 'treatments' as research: prospective customer perspectives from crowdfunding campaigns</strong></div><em>Regen. Med.</em> 2018; <strong>13</strong>:375-384</div><div class="external-links"><div class="core-xlink-crossref"><a href="https://doi.org/10.2217/rme-2018-0007" target="_blank" aria-label="Open Crossref in new tab">Crossref</a></div><div class="core-xlink-scopus"><a href="/servlet/linkout?suffix=e_1_5_1_2_9_2&dbid=137438953472&doi=10.1016%2Fj.jcyt.2023.03.002&key=2-s2.0-85049807873" target="_blank" aria-label="Open Scopus in new tab">Scopus (24)</a></div><div class="core-xlink-pubmed"><a href="https://pubmed.ncbi.nlm.nih.gov/29985757/" target="_blank" aria-label="Open PubMed in new tab">PubMed</a></div><div class="core-xlink-google-scholar"><a href="https://scholar.google.com/scholar_lookup?doi=10.2217%2Frme-2018-0007&pmid=29985757" target="_blank" aria-label="Open Google Scholar in new tab">Google Scholar</a></div></div></div></div></div><div role="listitem" data-has="label"><div id="bib0010" class="citations"><div id="sbref0010" class="citation"><div class="citation-content"><div class="label">10.</div><div>Sipp, D. ∙ Caulfield, T. ∙ Kaye, J. ...</div><div><strong>Marketing of unproven stem cell-based interventions: a call to action</strong></div><em>Sci Transl Med.</em> 2017; <strong>9</strong>, eaag0426</div><div class="external-links"><div class="core-xlink-crossref"><a href="https://doi.org/10.1126/scitranslmed.aag0426" target="_blank" aria-label="Open Crossref in new tab">Crossref</a></div><div class="core-xlink-scopus"><a href="/servlet/linkout?suffix=e_1_5_1_2_10_2&dbid=137438953472&doi=10.1016%2Fj.jcyt.2023.03.002&key=2-s2.0-85021874173" target="_blank" aria-label="Open Scopus in new tab">Scopus (145)</a></div><div class="core-xlink-pubmed"><a href="https://pubmed.ncbi.nlm.nih.gov/28679655/" target="_blank" aria-label="Open PubMed in new tab">PubMed</a></div><div class="core-xlink-google-scholar"><a href="https://scholar.google.com/scholar_lookup?doi=10.1126%2Fscitranslmed.aag0426&pmid=28679655" target="_blank" aria-label="Open Google Scholar in new tab">Google Scholar</a></div></div></div></div></div><div role="listitem" data-has="label"><div id="bib0011" class="citations"><div id="sbref0011" class="citation"><div class="citation-content"><div class="label">11.</div><div>Fink, D.W.</div><div><strong>FDA regulation of stem cell-based products</strong></div><em>Science.</em> 2009; <strong>324</strong>:1662-1663</div><div class="external-links"><div class="core-xlink-crossref"><a href="https://doi.org/10.1126/science.1173712" target="_blank" aria-label="Open Crossref in new tab">Crossref</a></div><div class="core-xlink-scopus"><a href="/servlet/linkout?suffix=e_1_5_1_2_11_2&dbid=137438953472&doi=10.1016%2Fj.jcyt.2023.03.002&key=2-s2.0-67649995222" target="_blank" aria-label="Open Scopus in new tab">Scopus (128)</a></div><div class="core-xlink-pubmed"><a href="https://pubmed.ncbi.nlm.nih.gov/19556496/" target="_blank" aria-label="Open PubMed in new tab">PubMed</a></div><div class="core-xlink-google-scholar"><a href="https://scholar.google.com/scholar_lookup?doi=10.1126%2Fscience.1173712&pmid=19556496" target="_blank" aria-label="Open Google Scholar in new tab">Google Scholar</a></div></div></div></div></div><div role="listitem" data-has="label"><div id="bib0012" class="citations"><div id="sbref0012" class="citation"><div class="citation-content"><div class="label">12.</div><div>Knoepfler, P.S.</div><div><strong>From bench to FDA to bedside: US regulatory trends for new stem cell therapies</strong></div><em>Adv Drug Deliv Rev.</em> 2015; <strong>82-83</strong>:192-196</div><div class="external-links"><div class="core-xlink-crossref"><a href="https://doi.org/10.1016/j.addr.2014.12.001" target="_blank" aria-label="Open Crossref in new tab">Crossref</a></div><div class="core-xlink-scopus"><a href="/servlet/linkout?suffix=e_1_5_1_2_12_2&dbid=137438953472&doi=10.1016%2Fj.jcyt.2023.03.002&key=2-s2.0-84927164105" target="_blank" aria-label="Open Scopus in new tab">Scopus (79)</a></div><div class="core-xlink-pubmed"><a href="https://pubmed.ncbi.nlm.nih.gov/25489841/" target="_blank" aria-label="Open PubMed in new tab">PubMed</a></div><div class="core-xlink-google-scholar"><a href="https://scholar.google.com/scholar_lookup?doi=10.1016%2Fj.addr.2014.12.001&pmid=25489841" target="_blank" aria-label="Open Google Scholar in new tab">Google Scholar</a></div></div></div></div></div><div role="listitem" data-has="label"><div id="bib0013" class="citations"><div id="sbref0013" class="citation"><div class="citation-content"><div class="label">13.</div><div><strong>Food & Drug Administration</strong></div>Regenerative Medicine Advanced Therapy Designation, 2021<div><a id="interref0034" href="https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/regenerative-medicine-advanced-therapy-designation" target="_blank">https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/regenerative-medicine-advanced-therapy-designation</a></div>(Accessed March 3 2023)</div><div class="external-links"><div class="core-xlink-google-scholar"><a href="https://scholar.google.com/scholar?q=Food+%26+Drug+Administration2021Regenerative+Medicine+Advanced+Therapy+Designationhttps%3A%2F%2Fwww.fda.gov%2Fvaccines-blood-biologics%2Fcellular-gene-therapy-products%2Fregenerative-medicine-advanced-therapy-designation%28Accessed+March+3+2023%29" target="_blank" aria-label="Open Google Scholar in new tab">Google Scholar</a></div></div></div></div></div><div role="listitem" data-has="label"><div id="bib0014" class="citations"><div id="sbref0014" class="citation"><div class="citation-content"><div class="label">14.</div><div>European Medicines Agency</div><div><strong>PRIME: priority medicines</strong></div>2021<div><a id="interref0035" href="https://www.ema.europa.eu/en/human-regulatory/research-development/prime-priority-medicines" target="_blank">https://www.ema.europa.eu/en/human-regulatory/research-development/prime-priority-medicines</a></div>(Accessed March 3 2023)</div><div class="external-links"><div class="core-xlink-google-scholar"><a href="https://scholar.google.com/scholar?q=European+Medicines+AgencyPRIME%3A+priority+medicines2021https%3A%2F%2Fwww.ema.europa.eu%2Fen%2Fhuman-regulatory%2Fresearch-development%2Fprime-priority-medicines%28Accessed+March+3+2023%29" target="_blank" aria-label="Open Google Scholar in new tab">Google Scholar</a></div></div></div></div></div><div role="listitem" data-has="label"><div id="bib0015" class="citations"><div id="sbref0015" class="citation"><div class="citation-content"><div class="label">15.</div><div>Ministry of Health, Labour and Welfare (MHLW)</div><div><strong>Strategy of SAKIGAKE</strong></div>2021<div><a id="interref0036" href="https://www.mhlw.go.jp/english/policy/health-medical/pharmaceuticals/140729-01.html" target="_blank">https://www.mhlw.go.jp/english/policy/health-medical/pharmaceuticals/140729-01.html</a></div>(Accessed March 3 2023)</div><div class="external-links"><div class="core-xlink-google-scholar"><a href="https://scholar.google.com/scholar?q=Ministry+of+Health%2C+Labour+and+Welfare+%28MHLW%29Strategy+of+SAKIGAKE2021https%3A%2F%2Fwww.mhlw.go.jp%2Fenglish%2Fpolicy%2Fhealth-medical%2Fpharmaceuticals%2F140729-01.html%28Accessed+March+3+2023%29" target="_blank" aria-label="Open Google Scholar in new tab">Google Scholar</a></div></div></div></div></div><div role="listitem" data-has="label"><div id="bib0016" class="citations"><div id="sbref0016" class="citation"><div class="citation-content"><div class="label">16.</div><div>Food & Drug Administration</div><div><strong>Approved cellular and gene therapy products</strong></div>2022<div><a id="interref0037" href="https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/approved-cellular-and-gene-therapy-products" target="_blank">https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/approved-cellular-and-gene-therapy-products</a></div>(Accessed March 3 2023)</div><div class="external-links"><div class="core-xlink-google-scholar"><a href="https://scholar.google.com/scholar?q=Food+%26+Drug+AdministrationApproved+cellular+and+gene+therapy+products2022https%3A%2F%2Fwww.fda.gov%2Fvaccines-blood-biologics%2Fcellular-gene-therapy-products%2Fapproved-cellular-and-gene-therapy-products%28Accessed+March+3+2023%29" target="_blank" aria-label="Open Google Scholar in new tab">Google Scholar</a></div></div></div></div></div><div role="listitem" data-has="label"><div id="bib0017" class="citations"><div id="sbref0017" class="citation"><div class="citation-content"><div class="label">17.</div><div>Cuende, N. ∙ Rasko, J.E.J. ∙ Koh, M.B.C. ...</div><div><strong>Cell, tissue and gene products with marketing authorization in 2018 worldwide</strong></div><em>Cytotherapy.</em> 2018; <strong>20</strong>:1401-1413</div><div class="external-links"><div class="core-xlink-fulltext"><a href="/servlet/linkout?suffix=e_1_5_1_2_17_2&dbid=4&doi=10.1016%2Fj.jcyt.2023.03.002&key=10.1016%2Fj.jcyt.2018.09.010&cf=fulltext&site=jcyt-site" target="_blank" aria-label="Open Full Text in new tab">Full Text</a></div><div class="core-xlink-pdf"><a href="/servlet/linkout?suffix=e_1_5_1_2_17_2&dbid=4&doi=10.1016%2Fj.jcyt.2023.03.002&key=10.1016%2Fj.jcyt.2018.09.010&cf=pdf&site=jcyt-site" target="_blank" aria-label="Open Full Text (PDF) in new tab">Full Text (PDF)</a></div><div class="core-xlink-scopus"><a href="/servlet/linkout?suffix=e_1_5_1_2_17_2&dbid=137438953472&doi=10.1016%2Fj.jcyt.2023.03.002&key=2-s2.0-85055293589" target="_blank" aria-label="Open Scopus in new tab">Scopus (87)</a></div><div class="core-xlink-pubmed"><a href="https://pubmed.ncbi.nlm.nih.gov/30366616/" target="_blank" aria-label="Open PubMed in new tab">PubMed</a></div><div class="core-xlink-google-scholar"><a href="https://scholar.google.com/scholar_lookup?doi=10.1016%2Fj.jcyt.2018.09.010&pmid=30366616" target="_blank" aria-label="Open Google Scholar in new tab">Google Scholar</a></div></div></div></div></div><div role="listitem" data-has="label"><div id="bib0018" class="citations"><div id="sbref0018" class="citation"><div class="citation-content"><div class="label">18.</div><div>Cuende, N. ∙ Boniface, C. ∙ Bravery, C. ...</div><div><strong>The puzzling situation of hospital exemption for advanced therapy medicinal products in Europe and stakeholders' concerns</strong></div><em>Cytotherapy.</em> 2014; <strong>16</strong>:1597-1600</div><div class="external-links"><div class="core-xlink-fulltext"><a href="/servlet/linkout?suffix=e_1_5_1_2_18_2&dbid=4&doi=10.1016%2Fj.jcyt.2023.03.002&key=10.1016%2Fj.jcyt.2014.08.007&cf=fulltext&site=jcyt-site" target="_blank" aria-label="Open Full Text in new tab">Full Text</a></div><div class="core-xlink-pdf"><a href="/servlet/linkout?suffix=e_1_5_1_2_18_2&dbid=4&doi=10.1016%2Fj.jcyt.2023.03.002&key=10.1016%2Fj.jcyt.2014.08.007&cf=pdf&site=jcyt-site" target="_blank" aria-label="Open Full Text (PDF) in new tab">Full Text (PDF)</a></div><div class="core-xlink-pubmed"><a href="https://pubmed.ncbi.nlm.nih.gov/25293816/" target="_blank" aria-label="Open PubMed in new tab">PubMed</a></div><div class="core-xlink-google-scholar"><a href="https://scholar.google.com/scholar_lookup?doi=10.1016%2Fj.jcyt.2014.08.007&pmid=25293816" target="_blank" aria-label="Open Google Scholar in new tab">Google Scholar</a></div></div></div></div></div><div role="listitem" data-has="label"><div id="bib0019" class="citations"><div id="sbref0019" class="citation"><div class="citation-content"><div class="label">19.</div><div>Cuende, N. ∙ Ciccocioppo, R. ∙ Forte, M. ...</div><div><strong>Patient access to and ethical considerations of the application of the European Union hospital exemption rule for advanced therapy medicinal products</strong></div><em>Cytotherapy.</em> 2022; <strong>24</strong>:686-690</div><div class="external-links"><div class="core-xlink-fulltext"><a href="/servlet/linkout?suffix=e_1_5_1_2_19_2&dbid=4&doi=10.1016%2Fj.jcyt.2023.03.002&key=10.1016%2Fj.jcyt.2022.03.007&cf=fulltext&site=jcyt-site" target="_blank" aria-label="Open Full Text in new tab">Full Text</a></div><div class="core-xlink-pdf"><a href="/servlet/linkout?suffix=e_1_5_1_2_19_2&dbid=4&doi=10.1016%2Fj.jcyt.2023.03.002&key=10.1016%2Fj.jcyt.2022.03.007&cf=pdf&site=jcyt-site" target="_blank" aria-label="Open Full Text (PDF) in new tab">Full Text (PDF)</a></div><div class="core-xlink-scopus"><a href="/servlet/linkout?suffix=e_1_5_1_2_19_2&dbid=137438953472&doi=10.1016%2Fj.jcyt.2023.03.002&key=2-s2.0-85129965189" target="_blank" aria-label="Open Scopus in new tab">Scopus (24)</a></div><div class="core-xlink-pubmed"><a href="https://pubmed.ncbi.nlm.nih.gov/35545453/" target="_blank" aria-label="Open PubMed in new tab">PubMed</a></div><div class="core-xlink-google-scholar"><a href="https://scholar.google.com/scholar_lookup?doi=10.1016%2Fj.jcyt.2022.03.007&pmid=35545453" target="_blank" aria-label="Open Google Scholar in new tab">Google Scholar</a></div></div></div></div></div><div role="listitem" data-has="label"><div id="bib0020" class="citations"><div id="sbref0020" class="citation"><div class="citation-content"><div class="label">20.</div><div>Marks, P. ∙ Gottlieb, S.</div><div><strong>Balancing safety and innovation for cell-based regenerative medicine</strong></div><em>N. Engl. J. Med.</em> 2018; <strong>378</strong>:954-959</div><div class="external-links"><div class="core-xlink-crossref"><a href="https://doi.org/10.1056/NEJMsr1715626" target="_blank" aria-label="Open Crossref in new tab">Crossref</a></div><div class="core-xlink-scopus"><a href="/servlet/linkout?suffix=e_1_5_1_2_20_2&dbid=137438953472&doi=10.1016%2Fj.jcyt.2023.03.002&key=2-s2.0-85043593239" target="_blank" aria-label="Open Scopus in new tab">Scopus (115)</a></div><div class="core-xlink-pubmed"><a href="https://pubmed.ncbi.nlm.nih.gov/29514023/" target="_blank" aria-label="Open PubMed in new tab">PubMed</a></div><div class="core-xlink-google-scholar"><a href="https://scholar.google.com/scholar_lookup?doi=10.1056%2FNEJMsr1715626&pmid=29514023" target="_blank" aria-label="Open Google Scholar in new tab">Google Scholar</a></div></div></div></div></div><div role="listitem" data-has="label"><div id="bib0021" class="citations"><div id="sbref0021" class="citation"><div class="citation-content"><div class="label">21.</div><div>Sipp, D. ∙ Sleeboom-Faulkner, M.</div><div><strong>Downgrading of regulation in regenerative medicine</strong></div><em>Science.</em> 2019; <strong>365</strong>:644-646</div><div class="external-links"><div class="core-xlink-crossref"><a href="https://doi.org/10.1126/science.aax6184" target="_blank" aria-label="Open Crossref in new tab">Crossref</a></div><div class="core-xlink-scopus"><a href="/servlet/linkout?suffix=e_1_5_1_2_21_2&dbid=137438953472&doi=10.1016%2Fj.jcyt.2023.03.002&key=2-s2.0-85070717645" target="_blank" aria-label="Open Scopus in new tab">Scopus (23)</a></div><div class="core-xlink-pubmed"><a href="https://pubmed.ncbi.nlm.nih.gov/31416952/" target="_blank" aria-label="Open PubMed in new tab">PubMed</a></div><div class="core-xlink-google-scholar"><a href="https://scholar.google.com/scholar_lookup?doi=10.1126%2Fscience.aax6184&pmid=31416952" target="_blank" aria-label="Open Google Scholar in new tab">Google Scholar</a></div></div></div></div></div><div role="listitem" data-has="label"><div id="bib0022" class="citations"><div id="sbref0022" class="citation"><div class="citation-content"><div class="label">22.</div><div>Bauer, G. ∙ Elsallab, M. ∙ Abou-El-Enein, M.</div><div><strong>Concise review: a comprehensive analysis of reported adverse events in patients receiving unproven stem cell-based interventions</strong></div><em>Stem Cells Transl. Med.</em> 2018; <strong>7</strong>:676-685</div><div class="external-links"><div class="core-xlink-crossref"><a href="https://doi.org/10.1002/sctm.17-0282" target="_blank" aria-label="Open Crossref in new tab">Crossref</a></div><div class="core-xlink-scopus"><a href="/servlet/linkout?suffix=e_1_5_1_2_22_2&dbid=137438953472&doi=10.1016%2Fj.jcyt.2023.03.002&key=2-s2.0-85052795693" target="_blank" aria-label="Open Scopus in new tab">Scopus (115)</a></div><div class="core-xlink-pubmed"><a href="https://pubmed.ncbi.nlm.nih.gov/30063299/" target="_blank" aria-label="Open PubMed in new tab">PubMed</a></div><div class="core-xlink-google-scholar"><a href="https://scholar.google.com/scholar_lookup?doi=10.1002%2Fsctm.17-0282&pmid=30063299" target="_blank" aria-label="Open Google Scholar in new tab">Google Scholar</a></div></div></div></div></div><div role="listitem" data-has="label"><div id="bib0023" class="citations"><div id="sbref0023" class="citation"><div class="citation-content"><div class="label">23.</div><div>Lysaght, T. ∙ Lipworth, W. ∙ Hendl, T. ...</div><div><strong>The deadly business of an unregulated global stem cell industry</strong></div><em>J. Med. Ethics.</em> 2017; <strong>43</strong>:744-746</div><div class="external-links"><div class="core-xlink-crossref"><a href="https://doi.org/10.1136/medethics-2016-104046" target="_blank" aria-label="Open Crossref in new tab">Crossref</a></div><div class="core-xlink-scopus"><a href="/servlet/linkout?suffix=e_1_5_1_2_23_2&dbid=137438953472&doi=10.1016%2Fj.jcyt.2023.03.002&key=2-s2.0-85032292795" target="_blank" aria-label="Open Scopus in new tab">Scopus (36)</a></div><div class="core-xlink-pubmed"><a href="https://pubmed.ncbi.nlm.nih.gov/28356490/" target="_blank" aria-label="Open PubMed in new tab">PubMed</a></div><div class="core-xlink-google-scholar"><a href="https://scholar.google.com/scholar_lookup?doi=10.1136%2Fmedethics-2016-104046&pmid=28356490" target="_blank" aria-label="Open Google Scholar in new tab">Google Scholar</a></div></div></div></div></div><div role="listitem" data-has="label"><div id="bib0024" class="citations"><div id="sbref0024" class="citation"><div class="citation-content"><div class="label">24.</div><div>Richardson, L.</div><div><strong>Harms Linked to Unapproved Stem Cell Interventions Highlight Need for Greater FDA Enforcement</strong></div>The Pew Charitable Trusts, 2021</div><div class="external-links"><div class="core-xlink-google-scholar"><a href="https://scholar.google.com/scholar?q=L.RichardsonHarms+Linked+to+Unapproved+Stem+Cell+Interventions+Highlight+Need+for+Greater+FDA+Enforcement2021The+Pew+Charitable+Trusts" target="_blank" aria-label="Open Google Scholar in new tab">Google Scholar</a></div></div></div></div></div><div role="listitem" data-has="label"><div id="bib0025" class="citations"><div id="sbref0025" class="citation"><div class="citation-content"><div class="label">25.</div>N. Ortolano, How do you separate scientifically sound stem cell therapies from scams?, 2020. <a id="interref0038" href="https://www.statnews.com/2020/08/18/separate-scientific-scam-stem-cell/" target="_blank">https://www.statnews.com/2020/08/18/separate-scientific-scam-stem-cell/</a>. (Accessed March 3 2023).</div><div class="external-links"><div class="core-xlink-google-scholar"><a href="https://scholar.google.com/scholar?q=N.+Ortolano%2C+How+do+you+separate+scientifically+sound+stem+cell+therapies+from+scams%3F%2C+2020.+https%3A%2F%2Fwww.statnews.com%2F2020%2F08%2F18%2Fseparate-scientific-scam-stem-cell%2F.+%28Accessed+March+3+2023%29." target="_blank" aria-label="Open Google Scholar in new tab">Google Scholar</a></div></div></div></div></div><div role="listitem" data-has="label"><div id="bib0026" class="citations"><div id="sbref0026" class="citation"><div class="citation-content"><div class="label">26.</div><div>Snyder, J. ∙ Turner, L. ∙ Crooks, V.A.</div><div><strong>Crowdfunding for unproven stem cell-based interventions</strong></div><em>JAMA-J. Am. Med. Assoc.</em> 2018; <strong>319</strong>:1935-1936</div><div class="external-links"><div class="core-xlink-crossref"><a href="https://doi.org/10.1001/jama.2018.3057" target="_blank" aria-label="Open Crossref in new tab">Crossref</a></div><div class="core-xlink-scopus"><a href="/servlet/linkout?suffix=e_1_5_1_2_26_2&dbid=137438953472&doi=10.1016%2Fj.jcyt.2023.03.002&key=2-s2.0-85046711618" target="_blank" aria-label="Open Scopus in new tab">Scopus (46)</a></div><div class="core-xlink-pubmed"><a href="https://pubmed.ncbi.nlm.nih.gov/29801003/" target="_blank" aria-label="Open PubMed in new tab">PubMed</a></div><div class="core-xlink-google-scholar"><a href="https://scholar.google.com/scholar_lookup?doi=10.1001%2Fjama.2018.3057&pmid=29801003" target="_blank" aria-label="Open Google Scholar in new tab">Google Scholar</a></div></div></div></div></div><div role="listitem" data-has="label"><div id="bib0027" class="citations"><div id="sbref0027" class="citation"><div class="citation-content"><div class="label">27.</div><div>European Medicines Agency (EMA)</div><div><strong>Committee for Advanced Therapies (CAT), EMA warns against using unproven cell-based therapies</strong></div>2020<div><a id="interref0039" href="https://www.ema.europa.eu/en/documents/public-statement/ema-warns-against-using-unproven-cell-based-therapies_en.pdf" target="_blank">https://www.ema.europa.eu/en/documents/public-statement/ema-warns-against-using-unproven-cell-based-therapies_en.pdf</a></div>(Accessed March 3 2023)</div><div class="external-links"><div class="core-xlink-google-scholar"><a href="https://scholar.google.com/scholar?q=European+Medicines+Agency+%28EMA%29Committee+for+Advanced+Therapies+%28CAT%29%2C+EMA+warns+against+using+unproven+cell-based+therapies2020https%3A%2F%2Fwww.ema.europa.eu%2Fen%2Fdocuments%2Fpublic-statement%2Fema-warns-against-using-unproven-cell-based-therapies_en.pdf%28Accessed+March+3+2023%29" target="_blank" aria-label="Open Google Scholar in new tab">Google Scholar</a></div></div></div></div></div><div role="listitem" data-has="label"><div id="bib0028" class="citations"><div id="sbref0028" class="citation"><div class="citation-content"><div class="label">28.</div><div>Food & Drug Administration</div><div><strong>FDA Warns About Stem Cell Therapies</strong></div>2019<div><a id="interref0040" href="https://www.fda.gov/consumers/consumer-updates/fda-warns-about-stem-cell-therapies" target="_blank">https://www.fda.gov/consumers/consumer-updates/fda-warns-about-stem-cell-therapies</a></div>(Accessed March 3 2023)</div><div class="external-links"><div class="core-xlink-google-scholar"><a href="https://scholar.google.com/scholar?q=Food+%26+Drug+AdministrationFDA+Warns+About+Stem+Cell+Therapies2019https%3A%2F%2Fwww.fda.gov%2Fconsumers%2Fconsumer-updates%2Ffda-warns-about-stem-cell-therapies%28Accessed+March+3+2023%29" target="_blank" aria-label="Open Google Scholar in new tab">Google Scholar</a></div></div></div></div></div><div role="listitem" data-has="label"><div id="bib0029" class="citations"><div id="sbref0029" class="citation"><div class="citation-content"><div class="label">29.</div><div>Hawke, B. ∙ Przybylo, A.R. ∙ Paciulli, D. ...</div><div><strong>How to peddle hope: an analysis of youtube patient testimonials of unproven stem cell treatments</strong></div><em>Stem Cell Rep.</em> 2019; <strong>12</strong>:1186-1189</div><div class="external-links"><div class="core-xlink-fulltext"><a href="/servlet/linkout?suffix=e_1_5_1_2_29_2&dbid=4&doi=10.1016%2Fj.jcyt.2023.03.002&key=10.1016%2Fj.stemcr.2019.05.009&cf=fulltext&site=cell-site" target="_blank" aria-label="Open Full Text in new tab">Full Text</a></div><div class="core-xlink-pdf"><a href="/servlet/linkout?suffix=e_1_5_1_2_29_2&dbid=4&doi=10.1016%2Fj.jcyt.2023.03.002&key=10.1016%2Fj.stemcr.2019.05.009&cf=pdf&site=cell-site" target="_blank" aria-label="Open Full Text (PDF) in new tab">Full Text (PDF)</a></div><div class="core-xlink-scopus"><a href="/servlet/linkout?suffix=e_1_5_1_2_29_2&dbid=137438953472&doi=10.1016%2Fj.jcyt.2023.03.002&key=2-s2.0-85066063194" target="_blank" aria-label="Open Scopus in new tab">Scopus (38)</a></div><div class="core-xlink-pubmed"><a href="https://pubmed.ncbi.nlm.nih.gov/31189092/" target="_blank" aria-label="Open PubMed in new tab">PubMed</a></div><div class="core-xlink-google-scholar"><a href="https://scholar.google.com/scholar_lookup?doi=10.1016%2Fj.stemcr.2019.05.009&pmid=31189092" target="_blank" aria-label="Open Google Scholar in new tab">Google Scholar</a></div></div></div></div></div><div role="listitem" data-has="label"><div id="bib0030" class="citations"><div id="sbref0030" class="citation"><div class="citation-content"><div class="label">30.</div><div>Dixon, Jr., J.R.</div><div><strong>The International Conference on Harmonization Good Clinical Practice guideline</strong></div><em>Qual Assur.</em> 1998; <strong>6</strong>:65-74</div><div class="external-links"><div class="core-xlink-crossref"><a href="https://doi.org/10.1080/105294199277860" target="_blank" aria-label="Open Crossref in new tab">Crossref</a></div><div class="core-xlink-pubmed"><a href="https://pubmed.ncbi.nlm.nih.gov/10386329/" target="_blank" aria-label="Open PubMed in new tab">PubMed</a></div><div class="core-xlink-google-scholar"><a href="https://scholar.google.com/scholar_lookup?doi=10.1080%2F105294199277860&pmid=10386329" target="_blank" aria-label="Open Google Scholar in new tab">Google Scholar</a></div></div></div></div></div><div role="listitem" data-has="label"><div id="bib0031" class="citations"><div id="sbref0031" class="citation"><div class="citation-content"><div class="label">31.</div><div><strong>Food & Drug Administration</strong></div>Consumer Alert on Regenerative Medicine Products Including Stem Cells and Exosomes, 2020<div><a id="interref0041" href="https://www.fda.gov/vaccines-blood-biologics/consumers-biologics/consumer-alert-regenerative-medicine-products-including-stem-cells-and-exosomes" target="_blank">https://www.fda.gov/vaccines-blood-biologics/consumers-biologics/consumer-alert-regenerative-medicine-products-including-stem-cells-and-exosomes</a></div>(Accessed March 3 2023)</div><div class="external-links"><div class="core-xlink-google-scholar"><a href="https://scholar.google.com/scholar?q=Food+%26+Drug+Administration2020Consumer+Alert+on+Regenerative+Medicine+Products+Including+Stem+Cells+and+Exosomeshttps%3A%2F%2Fwww.fda.gov%2Fvaccines-blood-biologics%2Fconsumers-biologics%2Fconsumer-alert-regenerative-medicine-products-including-stem-cells-and-exosomes%28Accessed+March+3+2023%29" target="_blank" aria-label="Open Google Scholar in new tab">Google Scholar</a></div></div></div></div></div><div role="listitem" data-has="label"><div id="bib0032" class="citations"><div id="sbref0032" class="citation"><div class="citation-content"><div class="label">32.</div><div>Turner, L. ∙ Munsie, M. ∙ Levine, A.D. ...</div><div><strong>Ethical issues and public communication in the development of cell-based treatments for COVID-19: lessons from the pandemic</strong></div><em>Stem Cell Rep.</em> 2021; <strong>16</strong>:2567-2576</div><div class="external-links"><div class="core-xlink-fulltext"><a href="/servlet/linkout?suffix=e_1_5_1_2_32_2&dbid=4&doi=10.1016%2Fj.jcyt.2023.03.002&key=10.1016%2Fj.stemcr.2021.09.005&cf=fulltext&site=cell-site" target="_blank" aria-label="Open Full Text in new tab">Full Text</a></div><div class="core-xlink-pdf"><a href="/servlet/linkout?suffix=e_1_5_1_2_32_2&dbid=4&doi=10.1016%2Fj.jcyt.2023.03.002&key=10.1016%2Fj.stemcr.2021.09.005&cf=pdf&site=cell-site" target="_blank" aria-label="Open Full Text (PDF) in new tab">Full Text (PDF)</a></div><div class="core-xlink-pubmed"><a href="https://pubmed.ncbi.nlm.nih.gov/34653406/" target="_blank" aria-label="Open PubMed in new tab">PubMed</a></div><div class="core-xlink-google-scholar"><a href="https://scholar.google.com/scholar_lookup?doi=10.1016%2Fj.stemcr.2021.09.005&pmid=34653406" target="_blank" aria-label="Open Google Scholar in new tab">Google Scholar</a></div></div></div></div></div><div role="listitem" data-has="label"><div id="bib0033" class="citations"><div id="sbref0033" class="citation"><div class="citation-content"><div class="label">33.</div><div>Levine, A.D. ∙ Wolf, L.E.</div><div><strong>The roles and responsibilities of physicians in patients' decisions about unproven stem cell therapies</strong></div><em>J. Law Med.Ethics.</em> 2012; <strong>40</strong>:122-134</div><div class="external-links"><div class="core-xlink-crossref"><a href="https://doi.org/10.1111/j.1748-720X.2012.00650.x" target="_blank" aria-label="Open Crossref in new tab">Crossref</a></div><div class="core-xlink-scopus"><a href="/servlet/linkout?suffix=e_1_5_1_2_33_2&dbid=137438953472&doi=10.1016%2Fj.jcyt.2023.03.002&key=2-s2.0-84859187160" target="_blank" aria-label="Open Scopus in new tab">Scopus (48)</a></div><div class="core-xlink-pubmed"><a href="https://pubmed.ncbi.nlm.nih.gov/22458467/" target="_blank" aria-label="Open PubMed in new tab">PubMed</a></div><div class="core-xlink-google-scholar"><a href="https://scholar.google.com/scholar_lookup?doi=10.1111%2Fj.1748-720X.2012.00650.x&pmid=22458467" target="_blank" aria-label="Open Google Scholar in new tab">Google Scholar</a></div></div></div></div></div><div role="listitem" data-has="label"><div id="bib0034" class="citations"><div id="sbref0034" class="citation"><div class="citation-content"><div class="label">34.</div><div>Weiss, D.J. ∙ Turner, L. ∙ Levine, A.D. ...</div><div><strong>Medical societies, patient education initiatives, public debate and marketing of unproven stem cell interventions</strong></div><em>Cytotherapy.</em> 2018; <strong>20</strong>:165-168</div><div class="external-links"><div class="core-xlink-fulltext"><a href="/servlet/linkout?suffix=e_1_5_1_2_34_2&dbid=4&doi=10.1016%2Fj.jcyt.2023.03.002&key=10.1016%2Fj.jcyt.2017.10.002&cf=fulltext&site=jcyt-site" target="_blank" aria-label="Open Full Text in new tab">Full Text</a></div><div class="core-xlink-pdf"><a href="/servlet/linkout?suffix=e_1_5_1_2_34_2&dbid=4&doi=10.1016%2Fj.jcyt.2023.03.002&key=10.1016%2Fj.jcyt.2017.10.002&cf=pdf&site=jcyt-site" target="_blank" aria-label="Open Full Text (PDF) in new tab">Full Text (PDF)</a></div><div class="core-xlink-scopus"><a href="/servlet/linkout?suffix=e_1_5_1_2_34_2&dbid=137438953472&doi=10.1016%2Fj.jcyt.2023.03.002&key=2-s2.0-85035124507" target="_blank" aria-label="Open Scopus in new tab">Scopus (20)</a></div><div class="core-xlink-pubmed"><a href="https://pubmed.ncbi.nlm.nih.gov/29239793/" target="_blank" aria-label="Open PubMed in new tab">PubMed</a></div><div class="core-xlink-google-scholar"><a href="https://scholar.google.com/scholar_lookup?doi=10.1016%2Fj.jcyt.2017.10.002&pmid=29239793" target="_blank" aria-label="Open Google Scholar in new tab">Google Scholar</a></div></div></div></div></div><div role="listitem" data-has="label"><div id="bib0035" class="citations"><div id="sbref0035" class="citation"><div class="citation-content"><div class="label">35.</div><div><strong>Health Canada</strong></div>Health Canada is advising Canadians about the potential health risks associated with unauthorized cell therapy treatments such as stem cell therapy, 2019<div><a id="interref0042" href="https://recalls-rappels.canada.ca/en/alert-recall/health-canada-advising-canadians-about-potential-health-risks-associated-unauthorized" target="_blank">https://recalls-rappels.canada.ca/en/alert-recall/health-canada-advising-canadians-about-potential-health-risks-associated-unauthorized</a></div>(Accessed March 3 2023)</div><div class="external-links"><div class="core-xlink-google-scholar"><a href="https://scholar.google.com/scholar?q=Health+Canada2019Health+Canada+is+advising+Canadians+about+the+potential+health+risks+associated+with+unauthorized+cell+therapy+treatments+such+as+stem+cell+therapyhttps%3A%2F%2Frecalls-rappels.canada.ca%2Fen%2Falert-recall%2Fhealth-canada-advising-canadians-about-potential-health-risks-associated-unauthorized%28Accessed+March+3+2023%29" target="_blank" aria-label="Open Google Scholar in new tab">Google Scholar</a></div></div></div></div></div><div role="listitem" data-has="label"><div id="bib0036" class="citations"><div id="sbref0036" class="citation"><div class="citation-content"><div class="label">36.</div><div><strong>Health Canada</strong></div>Health Canada Policy Position Paper – Autologous Cell Therapy Products, 2020<div><a id="interref0043" href="https://www.canada.ca/en/health-canada/services/drugs-health-products/biologics-radiopharmaceuticals-genetic-therapies/applications-submissions/guidance-documents/cell-therapy-policy.html" target="_blank">https://www.canada.ca/en/health-canada/services/drugs-health-products/biologics-radiopharmaceuticals-genetic-therapies/applications-submissions/guidance-documents/cell-therapy-policy.html</a></div>(Accessed March 3 2023)</div><div class="external-links"><div class="core-xlink-google-scholar"><a href="https://scholar.google.com/scholar?q=Health+Canada2020Health+Canada+Policy+Position+Paper+%E2%80%93+Autologous+Cell+Therapy+Productshttps%3A%2F%2Fwww.canada.ca%2Fen%2Fhealth-canada%2Fservices%2Fdrugs-health-products%2Fbiologics-radiopharmaceuticals-genetic-therapies%2Fapplications-submissions%2Fguidance-documents%2Fcell-therapy-policy.html%28Accessed+March+3+2023%29" target="_blank" aria-label="Open Google Scholar in new tab">Google Scholar</a></div></div></div></div></div><div role="listitem" data-has="label"><div id="bib0037" class="citations"><div id="sbref0037" class="citation"><div class="citation-content"><div class="label">37.</div>J.S. Eglovitch, WHO charts path to convergence on cell and gene therapies, 2022. <a id="interref0044" href="https://www.raps.org/news-and-articles/news-articles/2022/1/who-charts-path-to-convergence-on-cell-and-gene-th" target="_blank">https://www.raps.org/news-and-articles/news-articles/2022/1/who-charts-path-to-convergence-on-cell-and-gene-th</a>. (Accessed March 3 2023).</div><div class="external-links"><div class="core-xlink-google-scholar"><a href="https://scholar.google.com/scholar?q=J.S.+Eglovitch%2C+WHO+charts+path+to+convergence+on+cell+and+gene+therapies%2C+2022.+https%3A%2F%2Fwww.raps.org%2Fnews-and-articles%2Fnews-articles%2F2022%2F1%2Fwho-charts-path-to-convergence-on-cell-and-gene-th.+%28Accessed+March+3+2023%29." target="_blank" aria-label="Open Google Scholar in new tab">Google Scholar</a></div></div></div></div></div><div role="listitem" data-has="label"><div id="bib0038" class="citations"><div id="sbref0038" class="citation"><div class="citation-content"><div class="label">38.</div><div>Master, Z. ∙ Matthews, K.R.W. ∙ Abou-el-Enein, M.</div><div><strong>Unproven stem cell interventions: a global public health problem requiring global deliberation</strong></div><em>Stem Cell Rep.</em> 2021; <strong>16</strong>:1435-1445</div><div class="external-links"><div class="core-xlink-fulltext"><a href="/servlet/linkout?suffix=e_1_5_1_2_38_2&dbid=4&doi=10.1016%2Fj.jcyt.2023.03.002&key=10.1016%2Fj.stemcr.2021.05.004&cf=fulltext&site=cell-site" target="_blank" aria-label="Open Full Text in new tab">Full Text</a></div><div class="core-xlink-pdf"><a href="/servlet/linkout?suffix=e_1_5_1_2_38_2&dbid=4&doi=10.1016%2Fj.jcyt.2023.03.002&key=10.1016%2Fj.stemcr.2021.05.004&cf=pdf&site=cell-site" target="_blank" aria-label="Open Full Text (PDF) in new tab">Full Text (PDF)</a></div><div class="core-xlink-pubmed"><a href="https://pubmed.ncbi.nlm.nih.gov/34107243/" target="_blank" aria-label="Open PubMed in new tab">PubMed</a></div><div class="core-xlink-google-scholar"><a href="https://scholar.google.com/scholar_lookup?doi=10.1016%2Fj.stemcr.2021.05.004&pmid=34107243" target="_blank" aria-label="Open Google Scholar in new tab">Google Scholar</a></div></div></div></div></div><div role="listitem" data-has="label"><div id="bib0039" class="citations"><div id="sbref0039" class="citation"><div class="citation-content"><div class="label">39.</div><div>Vox, F. ∙ Folkers, K.M. ∙ Turi, A. ...</div><div><strong>Medical crowdfunding for scientifically unsupported or potentially dangerous treatments</strong></div><em>JAMA-J. Am. Med. Assoc.</em> 2018; <strong>320</strong>:1705-1706</div><div class="external-links"><div class="core-xlink-crossref"><a href="https://doi.org/10.1001/jama.2018.10264" target="_blank" aria-label="Open Crossref in new tab">Crossref</a></div><div class="core-xlink-scopus"><a href="/servlet/linkout?suffix=e_1_5_1_2_39_2&dbid=137438953472&doi=10.1016%2Fj.jcyt.2023.03.002&key=2-s2.0-85055464140" target="_blank" aria-label="Open Scopus in new tab">Scopus (40)</a></div><div class="core-xlink-pubmed"><a href="https://pubmed.ncbi.nlm.nih.gov/30357284/" target="_blank" aria-label="Open PubMed in new tab">PubMed</a></div><div class="core-xlink-google-scholar"><a href="https://scholar.google.com/scholar_lookup?doi=10.1001%2Fjama.2018.10264&pmid=30357284" target="_blank" aria-label="Open Google Scholar in new tab">Google Scholar</a></div></div></div></div></div><div role="listitem" data-has="label"><div id="bib0040" class="citations"><div id="sbref0040" class="citation"><div class="citation-content"><div class="label">40.</div><div>Knoepfler, P.S.</div><div><strong>The stem cell hard sell: report from a clinic's patient recruitment seminar</strong></div><em>Stem Cells Transl. Med.</em> 2017; <strong>6</strong>:14-16</div><div class="external-links"><div class="core-xlink-crossref"><a href="https://doi.org/10.5966/sctm.2016-0208" target="_blank" aria-label="Open Crossref in new tab">Crossref</a></div><div class="core-xlink-scopus"><a href="/servlet/linkout?suffix=e_1_5_1_2_40_2&dbid=137438953472&doi=10.1016%2Fj.jcyt.2023.03.002&key=2-s2.0-85017405858" target="_blank" aria-label="Open Scopus in new tab">Scopus (19)</a></div><div class="core-xlink-pubmed"><a href="https://pubmed.ncbi.nlm.nih.gov/28170181/" target="_blank" aria-label="Open PubMed in new tab">PubMed</a></div><div class="core-xlink-google-scholar"><a href="https://scholar.google.com/scholar_lookup?doi=10.5966%2Fsctm.2016-0208&pmid=28170181" target="_blank" aria-label="Open Google Scholar in new tab">Google Scholar</a></div></div></div></div></div><div role="listitem" data-has="label"><div id="bib0041" class="citations"><div id="sbref0041" class="citation"><div class="citation-content"><div class="label">41.</div><div>Wan, W. ∙ McGinley, L.</div><div><strong>Clinic pitches unproven treatments to desperate patients, with tips on raising the cash</strong></div>Washington Post, 2019</div><div class="external-links"><div class="core-xlink-google-scholar"><a href="https://scholar.google.com/scholar?q=W.WanL.McGinleyClinic+pitches+unproven+treatments+to+desperate+patients%2C+with+tips+on+raising+the+cash2019Washington+Post" target="_blank" aria-label="Open Google Scholar in new tab">Google Scholar</a></div></div></div></div></div><div role="listitem" data-has="label"><div id="bib0042" class="citations"><div id="sbref0042" class="citation"><div class="citation-content"><div class="label">42.</div><div>Marks, P.W. ∙ Hahn, S.</div><div><strong>Identifying the risks of unproven regenerative medicine therapies</strong></div><em>JAMA-J. Am. Med. Assoc.</em> 2020; <strong>324</strong>:241-242</div><div class="external-links"><div class="core-xlink-crossref"><a href="https://doi.org/10.1001/jama.2020.9375" target="_blank" aria-label="Open Crossref in new tab">Crossref</a></div><div class="core-xlink-scopus"><a href="/servlet/linkout?suffix=e_1_5_1_2_42_2&dbid=137438953472&doi=10.1016%2Fj.jcyt.2023.03.002&key=2-s2.0-85086877743" target="_blank" aria-label="Open Scopus in new tab">Scopus (21)</a></div><div class="core-xlink-pubmed"><a href="https://pubmed.ncbi.nlm.nih.gov/32629463/" target="_blank" aria-label="Open PubMed in new tab">PubMed</a></div><div class="core-xlink-google-scholar"><a href="https://scholar.google.com/scholar_lookup?doi=10.1001%2Fjama.2020.9375&pmid=32629463" target="_blank" aria-label="Open Google Scholar in new tab">Google Scholar</a></div></div></div></div></div><div role="listitem" data-has="label"><div id="bib0043" class="citations"><div id="sbref0043" class="citation"><div class="citation-content"><div class="label">43.</div><div>Fu, W. ∙ Smith, C. ∙ Turner, L. ...</div><div><strong>Characteristics and scope of training of clinicians participating in the US direct-to-consumer marketplace for unproven stem cell interventions</strong></div><em>JAMA-J. Am. Med. Assoc.</em> 2019; <strong>321</strong>:2462-2463</div><div class="external-links"><div class="core-xlink-crossref"><a href="https://doi.org/10.1001/jama.2019.5837" target="_blank" aria-label="Open Crossref in new tab">Crossref</a></div><div class="core-xlink-scopus"><a href="/servlet/linkout?suffix=e_1_5_1_2_43_2&dbid=137438953472&doi=10.1016%2Fj.jcyt.2023.03.002&key=2-s2.0-85068040816" target="_blank" aria-label="Open Scopus in new tab">Scopus (25)</a></div><div class="core-xlink-google-scholar"><a href="https://scholar.google.com/scholar_lookup?doi=10.1001%2Fjama.2019.5837" target="_blank" aria-label="Open Google Scholar in new tab">Google Scholar</a></div></div></div></div></div><div role="listitem" data-has="label"><div id="bib0044" class="citations"><div id="sbref0044" class="citation"><div class="citation-content"><div class="label">44.</div><div>Ogbogu, U. ∙ Du, J. ∙ Koukio, Y.</div><div><strong>The involvement of Canadian physicians in promoting and providing unproven and unapproved stem cell interventions</strong></div><em>BMC Med Ethics.</em> 2018; <strong>19</strong>, 32</div><div class="external-links"><div class="core-xlink-crossref"><a href="https://doi.org/10.1186/s12910-018-0273-6" target="_blank" aria-label="Open Crossref in new tab">Crossref</a></div><div class="core-xlink-scopus"><a href="/servlet/linkout?suffix=e_1_5_1_2_44_2&dbid=137438953472&doi=10.1016%2Fj.jcyt.2023.03.002&key=2-s2.0-85046247236" target="_blank" aria-label="Open Scopus in new tab">Scopus (20)</a></div><div class="core-xlink-pubmed"><a href="https://pubmed.ncbi.nlm.nih.gov/29716594/" target="_blank" aria-label="Open PubMed in new tab">PubMed</a></div><div class="core-xlink-google-scholar"><a href="https://scholar.google.com/scholar_lookup?doi=10.1186%2Fs12910-018-0273-6&pmid=29716594" target="_blank" aria-label="Open Google Scholar in new tab">Google Scholar</a></div></div></div></div></div><div role="listitem" data-has="label"><div id="bib0045" class="citations"><div id="sbref0045" class="citation"><div class="citation-content"><div class="label">45.</div><div>Turner, L. ∙ Knoepfler, P.</div><div><strong>Selling stem cells in the USA: assessing the direct-to-consumer industry</strong></div><em>Cell Stem Cell.</em> 2016; <strong>19</strong>:154-157</div><div class="external-links"><div class="core-xlink-fulltext"><a href="/servlet/linkout?suffix=e_1_5_1_2_45_2&dbid=4&doi=10.1016%2Fj.jcyt.2023.03.002&key=10.1016%2Fj.stem.2016.06.007&cf=fulltext&site=cell-site" target="_blank" aria-label="Open Full Text in new tab">Full Text</a></div><div class="core-xlink-pdf"><a href="/servlet/linkout?suffix=e_1_5_1_2_45_2&dbid=4&doi=10.1016%2Fj.jcyt.2023.03.002&key=10.1016%2Fj.stem.2016.06.007&cf=pdf&site=cell-site" target="_blank" aria-label="Open Full Text (PDF) in new tab">Full Text (PDF)</a></div><div class="core-xlink-scopus"><a href="/servlet/linkout?suffix=e_1_5_1_2_45_2&dbid=137438953472&doi=10.1016%2Fj.jcyt.2023.03.002&key=2-s2.0-84978493321" target="_blank" aria-label="Open Scopus in new tab">Scopus (275)</a></div><div class="core-xlink-pubmed"><a href="https://pubmed.ncbi.nlm.nih.gov/27374789/" target="_blank" aria-label="Open PubMed in new tab">PubMed</a></div><div class="core-xlink-google-scholar"><a href="https://scholar.google.com/scholar_lookup?doi=10.1016%2Fj.stem.2016.06.007&pmid=27374789" target="_blank" aria-label="Open Google Scholar in new tab">Google Scholar</a></div></div></div></div></div><div role="listitem" data-has="label"><div id="bib0046" class="citations"><div id="sbref0046" class="citation"><div class="citation-content"><div class="label">46.</div>C. Kelly, ‘FTC weighing trade rule on fake endorsements, including by ‘patient ambassadors’, 2020. <a id="interref0045" href="https://pink.pharmaintelligence.informa.com/PS147174/FTC-Weighing-Trade-Rule-On-Fake-Endorsements-Including-By-Patient-Ambassadors" target="_blank">https://pink.pharmaintelligence.informa.com/PS147174/FTC-Weighing-Trade-Rule-On-Fake-Endorsements-Including-By-Patient-Ambassadors</a>. (Accessed March 3 2023).</div><div class="external-links"><div class="core-xlink-google-scholar"><a href="https://scholar.google.com/scholar?q=C.+Kelly%2C+%E2%80%98FTC+weighing+trade+rule+on+fake+endorsements%2C+including+by+%E2%80%98patient+ambassadors%E2%80%99%2C+2020.+https%3A%2F%2Fpink.pharmaintelligence.informa.com%2FPS147174%2FFTC-Weighing-Trade-Rule-On-Fake-Endorsements-Including-By-Patient-Ambassadors.+%28Accessed+March+3+2023%29." target="_blank" aria-label="Open Google Scholar in new tab">Google Scholar</a></div></div></div></div></div><div role="listitem" data-has="label"><div id="bib0047" class="citations"><div id="sbref0047" class="citation"><div class="citation-content"><div class="label">47.</div><div>Caulfield, T. ∙ Sipp, D. ∙ Murry, C.E. ...</div><div><strong>Confronting stem cell hype</strong></div><em>Science.</em> 2016; <strong>352</strong>:776-777</div><div class="external-links"><div class="core-xlink-crossref"><a href="https://doi.org/10.1126/science.aaf4620" target="_blank" aria-label="Open Crossref in new tab">Crossref</a></div><div class="core-xlink-scopus"><a href="/servlet/linkout?suffix=e_1_5_1_2_47_2&dbid=137438953472&doi=10.1016%2Fj.jcyt.2023.03.002&key=2-s2.0-84969217686" target="_blank" aria-label="Open Scopus in new tab">Scopus (111)</a></div><div class="core-xlink-pubmed"><a href="https://pubmed.ncbi.nlm.nih.gov/27174977/" target="_blank" aria-label="Open PubMed in new tab">PubMed</a></div><div class="core-xlink-google-scholar"><a href="https://scholar.google.com/scholar_lookup?doi=10.1126%2Fscience.aaf4620&pmid=27174977" target="_blank" aria-label="Open Google Scholar in new tab">Google Scholar</a></div></div></div></div></div></div></div></section></div></section><div class="core-linked-content"> </div></div></div><div class="core-collateral-aside"><section id="core-collateral-figures"></section> <section id="core-collateral-metrics" class="publication-list__axel-section"><h2>Article metrics</h2><div><ul class="publication-list rlist publication-list--list plum-x--lazy-load publication-list--axel" data-plum-x-url="/pb/widgets/ux3/publicationList/plumx?widgetId=60784550-ac83-412a-a4dd-0b020b0cfaed&pbContext=%3Bissue%3Aissue%3Apii%5C%3AS1465324922X00224%3Bctype%3Astring%3AJournal+Content%3BrequestedJournal%3Ajournal%3Ajcyt%3Barticle%3Aarticle%3Apii%5C%3AS1465324923000646%3Bwebsite%3Awebsite%3Ajcyt-site%3BpageGroup%3Astring%3AArticle+View%3Bjournal%3Ajournal%3Ajcyt%3Bwgroup%3Astring%3AMigrated+Websites%3Bpage%3Astring%3AShow+Full+Text%3BsubPage%3Astring%3AFull+Text%3Bproduct%3Aproduct%3Aelsevier%5C%3Aproduct%5C%3Aha" data-pb-mode-enabled="false"><li aria-label="loading articles" role="alert" class="js--loading plum-x--spinner hidden"></li></ul></div></section> <section id="core-collateral-supplementary"></section> <section id="core-collateral-relatedArticles" class="axel-related-articles"><h2 id="relatedArticles" class="top axel-related-articles__title" data-title="Related articles">Related Articles</h2><div data-pb-widget-type="ux3-relatedArticles" data-widget-id="55d12544-88af-4b41-92cd-fa404a51ef23" data-widget-name="AtyponTempUX3RelatedArticlesWidget" data-article-pii="S1465324923000646" class="ux3DeferredOnScrollWidget axel-related-articles__body" data-show-more="true"></div></section> </div></div><aside data-core-aside="right-rail"><div class="inner-wrapper"> <div class="widget literatumAd none adplaceholder widget-verticalAd" id="80e61381-d1dc-4a1f-98c4-59c9e22b2cf2"> <div class="wrapped " > <div class="widget-body body body-verticalAd "><div class="verticalAdContainer"> <div class="verticalAdLabelContainer"> <div class="verticalAdLabel"> <img src="/templates/jsp/_style2/_marlin/images/bg_adVert.gif" alt="Advertisement"/> </div> </div> <div class="verticalAd"> <div class="pb-ad"> <div class="gpt-ad" data-adsize="sidebar"></div> </div> </div> </div></div> </div> </div> </div></aside><div class="core-authors-details" style="display:none"><section class="core-authors"><div id="au0001" property="author" typeof="Person"><div class="heading"><span property="givenName">Laertis</span> <span property="familyName">Ikonomou</span> <a class="orcid-id" href="https://orcid.org/0000-0003-0993-6713" property="identifier" aria-label="ORCID identifier" target="_blank">0000-0003-0993-6713</a></div><div class="content"><div class="core-author-emails"><div class="label">Correspondence</div><div>Correspondence: Laertis Ikonomou, PhD, Department of Oral Biology, University at Buffalo, The State University of New York, 619 Biomedical Research Building (BRB), South Campus, Buffalo, NY 14214-8024.</div><div><a id="ead0001" href="mailto:laertisi@buffalo.edu" property="email" title="Send email to Laertis Ikonomou">laertisi@buffalo.edu</a></div></div><div class="core-author-affiliations"><div class="label">Affiliations</div><div property="affiliation" typeof="Organization"><span property="name">Department of Oral Biology, University at Buffalo, The State University of New York, Buffalo, New York, USA</span></div><div property="affiliation" typeof="Organization"><span property="name">Cell, Gene and Tissue Engineering Center, University at Buffalo, The State University of New York, Buffalo, New York, USA</span></div></div><div class="core-author-link"><a href="/authored-by/Ikonomou/Laertis" target="_blank">Search for articles by this author</a></div></div></div><div id="au0002" property="author" typeof="Person"><div class="heading"><span property="givenName">Natividad</span> <span property="familyName">Cuende</span></div><div class="content"><div class="core-author-notes"><div class="label">Footnotes</div><div role="doc-footnote" data-has="label"><div class="label">⁎⁎</div><div id="fn1"><div id="notep0001" role="paragraph">These authors have contributed equally to this work and should be considered second co-authors</div></div></div></div><div class="core-author-affiliations"><div class="label">Affiliations</div><div property="affiliation" typeof="Organization"><span property="name">Andalusian Transplant Coordination, Servicio Andaluz de Salud; Sevilla, Spain</span></div></div><div class="core-author-link"><a href="/authored-by/Cuende/Natividad" target="_blank">Search for articles by this author</a></div></div></div><div id="au0003" property="author" typeof="Person"><div class="heading"><span property="givenName">Miguel</span> <span property="familyName">Forte</span> <a class="orcid-id" href="https://orcid.org/0000-0002-0584-0389" property="identifier" aria-label="ORCID identifier" target="_blank">0000-0002-0584-0389</a></div><div class="content"><div class="core-author-notes"><div class="label">Footnotes</div><div role="doc-footnote" data-has="label"><div class="label">⁎⁎</div><div id="fn1"><div id="notep0001" role="paragraph">These authors have contributed equally to this work and should be considered second co-authors</div></div></div></div><div class="core-author-affiliations"><div class="label">Affiliations</div><div property="affiliation" typeof="Organization"><span property="name">AdBio Partners, Paris, France</span></div></div><div class="core-author-link"><a href="/authored-by/Forte/Miguel" target="_blank">Search for articles by this author</a></div></div></div><div id="au0004" property="author" typeof="Person"><div class="heading"><span property="givenName">Bambi J.</span> <span property="familyName">Grilley</span></div><div class="content"><div class="core-author-notes"><div class="label">Footnotes</div><div role="doc-footnote" data-has="label"><div class="label">⁎⁎</div><div id="fn1"><div id="notep0001" role="paragraph">These authors have contributed equally to this work and should be considered second co-authors</div></div></div></div><div class="core-author-affiliations"><div class="label">Affiliations</div><div property="affiliation" typeof="Organization"><span property="name">Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, Houston Methodist Hospital, Houston, Texas, USA</span></div><div property="affiliation" typeof="Organization"><span property="name">Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA</span></div></div><div class="core-author-link"><a href="/authored-by/Grilley/Bambi+J" target="_blank">Search for articles by this author</a></div></div></div><div id="au0005" property="author" typeof="Person"><div class="heading"><span property="givenName">Aaron D.</span> <span property="familyName">Levine</span></div><div class="content"><div class="core-author-notes"><div class="label">Footnotes</div><div role="doc-footnote" data-has="label"><div class="label">⁎⁎</div><div id="fn1"><div id="notep0001" role="paragraph">These authors have contributed equally to this work and should be considered second co-authors</div></div></div></div><div class="core-author-affiliations"><div class="label">Affiliations</div><div property="affiliation" typeof="Organization"><span property="name">School of Public Policy, Georgia Institute of Technology, Atlanta, Georgia, USA</span></div></div><div class="core-author-link"><a href="/authored-by/Levine/Aaron+D" target="_blank">Search for articles by this author</a></div></div></div><div id="au0006" property="author" typeof="Person"><div class="heading"><span property="givenName">Megan</span> <span property="familyName">Munsie</span></div><div class="content"><div class="core-author-notes"><div class="label">Footnotes</div><div role="doc-footnote" data-has="label"><div class="label">⁎⁎</div><div id="fn1"><div id="notep0001" role="paragraph">These authors have contributed equally to this work and should be considered second co-authors</div></div></div></div><div class="core-author-affiliations"><div class="label">Affiliations</div><div property="affiliation" typeof="Organization"><span property="name">Melbourne Medical School, University of Melbourne, Parkville, Victoria, Australia</span></div><div property="affiliation" typeof="Organization"><span property="name">Murdoch Children's Research Institute, Parkville, Victoria, Australia</span></div></div><div class="core-author-link"><a href="/authored-by/Munsie/Megan" target="_blank">Search for articles by this author</a></div></div></div><div id="au0007" property="author" typeof="Person"><div class="heading"><span property="givenName">John E.J.</span> <span property="familyName">Rasko</span> <a class="orcid-id" href="https://orcid.org/0000-0003-2975-807X" property="identifier" aria-label="ORCID identifier" target="_blank">0000-0003-2975-807X</a></div><div class="content"><div class="core-author-notes"><div class="label">Footnotes</div><div role="doc-footnote" data-has="label"><div class="label">⁎⁎</div><div id="fn1"><div id="notep0001" role="paragraph">These authors have contributed equally to this work and should be considered second co-authors</div></div></div></div><div class="core-author-affiliations"><div class="label">Affiliations</div><div property="affiliation" typeof="Organization"><span property="name">Gene and Stem Cell Therapy Program Centenary Institute, University of Sydney, Sydney, NSW, Australia</span></div><div property="affiliation" typeof="Organization"><span property="name">Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia</span></div><div property="affiliation" typeof="Organization"><span property="name">Cell & Molecular Therapies, Royal Prince Alfred Hospital, Camperdown, NSW, Australia</span></div></div><div class="core-author-link"><a href="/authored-by/Rasko/John+E+J" target="_blank">Search for articles by this author</a></div></div></div><div id="au0008" property="author" typeof="Person"><div class="heading"><span property="givenName">Leigh</span> <span property="familyName">Turner</span> <a class="orcid-id" href="https://orcid.org/0000-0001-7283-6809" property="identifier" aria-label="ORCID identifier" target="_blank">0000-0001-7283-6809</a></div><div class="content"><div class="core-author-notes"><div class="label">Footnotes</div><div role="doc-footnote" data-has="label"><div class="label">⁎⁎</div><div id="fn1"><div id="notep0001" role="paragraph">These authors have contributed equally to this work and should be considered second co-authors</div></div></div></div><div class="core-author-affiliations"><div class="label">Affiliations</div><div property="affiliation" typeof="Organization"><span property="name">Department of Health, Society, and Behavior, Program in Public Health; Stem Cell Research Center; Institute for Clinical and Translational Science; Department of Family Medicine; University of California, Irvine; Irvine, California, USA</span></div></div><div class="core-author-link"><a href="/authored-by/Turner/Leigh" target="_blank">Search for articles by this author</a></div></div></div><div id="au0009" property="author" typeof="Person"><div class="heading"><span property="givenName">Hamid R.</span> <span property="familyName">Bidkhori</span> <a class="orcid-id" href="https://orcid.org/0000-0002-0204-0351" property="identifier" aria-label="ORCID identifier" target="_blank">0000-0002-0204-0351</a></div><div class="content"><div class="core-author-affiliations"><div class="label">Affiliations</div><div property="affiliation" typeof="Organization"><span property="name">Stem Cell and Regenerative Medicine Research Department, Academic Center for Education, Culture and Research (ACECR)-Khorasan Razavi, Mashhad, Iran</span></div></div><div class="core-author-link"><a href="/authored-by/Bidkhori/Hamid+R" target="_blank">Search for articles by this author</a></div></div></div><div id="au0010" property="author" typeof="Person"><div class="heading"><span property="givenName">Rachele</span> <span property="familyName">Ciccocioppo</span> <a class="orcid-id" href="https://orcid.org/0000-0002-6297-7576" property="identifier" aria-label="ORCID identifier" target="_blank">0000-0002-6297-7576</a></div><div class="content"><div class="core-author-affiliations"><div class="label">Affiliations</div><div property="affiliation" typeof="Organization"><span property="name">Gastroenterology Unit, Department of Medicine, A.O.U.I. Policlinico G.B. Rossi & University of Verona, Verona, Italy</span></div></div><div class="core-author-link"><a href="/authored-by/Ciccocioppo/Rachele" target="_blank">Search for articles by this author</a></div></div></div><div id="au0011" property="author" typeof="Person"><div class="heading"><span property="givenName">Felix</span> <span property="familyName">Grignon</span></div><div class="content"><div class="core-author-affiliations"><div class="label">Affiliations</div><div property="affiliation" typeof="Organization"><span property="name">International Society for Cell & Gene Therapy, Vancouver, Canada</span></div></div><div class="core-author-link"><a href="/authored-by/Grignon/Felix" target="_blank">Search for articles by this author</a></div></div></div><div id="au0012" property="author" typeof="Person"><div class="heading"><span property="givenName">Alok</span> <span property="familyName">Srivastava</span></div><div class="content"><div class="core-author-affiliations"><div class="label">Affiliations</div><div property="affiliation" typeof="Organization"><span property="name">Department of Haematology, Christian Medical College, Ranipet Campus, Ranipet & Centre for Stem Cell Research (a unit of inStem Bengaluru) CMC Campus, Vellore, India</span></div></div><div class="core-author-link"><a href="/authored-by/Srivastava/Alok" target="_blank">Search for articles by this author</a></div></div></div><div id="au0013" property="author" typeof="Person"><div class="heading"><span property="givenName">Daniel J.</span> <span property="familyName">Weiss</span></div><div class="content"><div class="core-author-affiliations"><div class="label">Affiliations</div><div property="affiliation" typeof="Organization"><span property="name">University of Vermont College of Medicine, Burlington, Vermont, USA</span></div></div><div class="core-author-link"><a href="/authored-by/Weiss/Daniel+J" target="_blank">Search for articles by this author</a></div></div></div><div id="au0014" property="author" typeof="Person"><div class="heading"><span property="givenName">Patricia</span> <span property="familyName">Zettler</span> <a class="orcid-id" href="https://orcid.org/0000-0001-9114-0735" property="identifier" aria-label="ORCID identifier" target="_blank">0000-0001-9114-0735</a></div><div class="content"><div class="core-author-affiliations"><div class="label">Affiliations</div><div property="affiliation" typeof="Organization"><span property="name">Moritz College of Law, Drug Enforcement and Policy Center, Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA</span></div></div><div class="core-author-link"><a href="/authored-by/Zettler/Patricia" target="_blank">Search for articles by this author</a></div></div></div><div id="au0015" property="author" typeof="Person"><div class="heading"><span property="givenName">Bruce L.</span> <span property="familyName">Levine</span></div><div class="content"><div class="core-author-notes"><div class="label">Footnotes</div><div role="doc-footnote" data-has="label"><div class="label">⁎⁎⁎</div><div id="fn2"><div id="notep0002" role="paragraph">Senior author.</div></div></div></div><div class="core-author-affiliations"><div class="label">Affiliations</div><div property="affiliation" typeof="Organization"><span property="name">Center for Cellular Immunotherapies, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, Pennsylvania, USA</span></div></div><div class="core-author-link"><a href="/authored-by/Levine/Bruce+L" target="_blank">Search for articles by this author</a></div></div></div><div id="au0016" property="author" typeof="Person"><div class="heading"><span property="name">ISCT Committee on the Ethics of Cell and Gene Therapy (ECGT)</span></div><div class="content"><div class="core-author-link"><a href="/authored-by/group/ISCT+Committee+on+the+Ethics+of+Cell+and+Gene+Therapy+%28ECGT%29" target="_blank">Search for articles by this author</a></div></div></div></section></div></article><div data-extent="article-wrapper"><div class="core-container"></div></div><script id="contribution-meta" type="application/json">{ "doi": "10.1016/j.jcyt.2023.03.002", "isRetraction": "false", "isRetired": "false" }</script><script type="text/javascript" defer="defer" src="https://static.addtoany.com/menu/page.js" class="optanon-category-C0004 ot-vscat-C0004"></script><script id="book-title" type="application/json">{ "bookTitle": "" } </script><template id="figure_nav_template"><a href="#" class="open-in-viewer btn btn-dark figure-pop-btn"><i aria-hidden="true" class="icon-export_citation"></i><span>Open in viewer</span></a></template><div id="figure-viewer" role="dialog" aria-modal="true" aria-label="Figure Viewer" class="showCaption showThumbstrip figure-viewer"><nav class="nav-bar figure-viewer__top"><a href="#" title="Close Figure Viewer" role="button" class="figure-viewer__close"><i aria-hidden="true" class="icon-tools_close"></i></a><div class="figure-viewer__title"></div></nav><div class="frames"><ul class="frames__list"></ul><a href="#" title="Previous Frame" class="frameButton previousFrameButton frames__prev"><i class="icon-arrow_l"></i></a><a href="#" title="Next Frame" class="frameButton nextFrameButton frames__next"><i class="icon-arrow_r"></i></a></div><div class="caption"><div class="figure-viewer__caption-body"></div></div><div class="toolbar figure-viewer__toolbar"><span class="figure-viewer__counter"></span><a href="#" class="button toggle-caption-button figure-viewer__caption__ctrl"><i aria-hidden="true" class="icon icon-info"></i><span class="label">Hide Caption</span></a><a href="#" class="button download-options-button"><i aria-hidden="true" class="icon icon-gizmo-folder-in download-size-icon"></i><span class="label">Download</span></a><a href="#figures" class="button see-figures figure-viewer__see-figure__ctrl"><i aria-hidden="true" class="icon icon-gizmo-image_figure viewer-size-icon"></i><span class="label">See figure in Article</span></a></div><div class="thumbstrip"><a href="#" class="toggleButton thumbstrip__ctrl"><span>Toggle Thumbstrip</span></a><a href="#" title="Previous Thumbnails" class="thumbstripButton previousThumbstripButton thumbstrip__prev"><i aria-hidden="true" class="icon-arrow_l"></i></a><a href="#" title="Next Thumbnails" class="thumbstripButton nextThumbstripButton thumbstrip__next"><i aria-hidden="true" class="icon-arrow_r"></i></a><div class="thumbstrip__wrapper"><ul class="rlist figure-viewer__thumbslist"></ul></div></div><div class="download figure-viewer__download"><div class="pointer"></div><ul class="rlist downlad__wrapper"><li><a target="_blank" href="/specs/products/marlin/components/figure-viewer/images/facets-2015-0010-f10-standard.jpg" title="View high resolution image in a new tab" class="downloadThisButton"><i class="icon icon-gizmo-image_figure figure-viewer__download__viewer-size-icon"></i><span class="figure-viewer__download__text">Download Hi-res image</span></a></li><li class="hidden-xs hidden-sm"><a href="/action/downloadFigures?articleNumber=e00489" target="_blank" title="Doanload .PPT" class="downloadAllButton"><i class="icon icon-gizmo-ppt figure-viewer__download__viewer-size-icon figure-viewer__download__viewer-size-icon--ppt"></i><span class="figure-viewer__download__text"> Download .PPT</span></a></li></ul></div></div><template id="toCitationLink" data-citation="Citation" data-footnote="Footnote"><div class="to-citation__wrapper"><a class="to-citation"><i aria-hidden="true" class="icon-subdirectory_arrow_left"></i><span>Go to</span></a></div></template><template id="toCitationButton" data-citation="Citation" data-footnote="Footnote"><div class="to-citation__wrapper"><button class="to-citation"><i aria-hidden="true" class="icon-subdirectory_arrow_left"></i><span>Go to</span></button></div></template><template id="toCitationAccordion" data-collapse-citation="Hide Citations" data-expand-citation="Show Citations" data-collapse-footnote="Hide Footnotes" data-expand-footnote="Show Footnotes"><div class="to-citation__wrapper"><button aria-controls="aria-controls" aria-expanded="false" aria-haspopup="true" aria-label="Toggle citations menu" class="to-citation__toggle"><i aria-hidden="true" class="icon-plus"></i><span data-expand-title="data-expand-title" data-collapsed-title="data-collapsed-title" class="accordion__toggle__title"></span></button><div role="menu" aria-label="links" class="to-citation__accordion no-separator"><ul></ul></div></div></template><template id="toCitationAccordionItem"><li><a class="to-citation"><i aria-hidden="true" class="icon-subdirectory_arrow_left"></i><span></span></a></li></template><template id="citations_truncate_template"><div class="citations-truncation"><button data-label-expand="Show all references" data-label-collapse="Show fewer" data-label-remaining="references remaining" class="btn btn--inverse"><span>Show all references</span></button></div></template><template id="collateral_texts_template" data-do="Digital Object" data-figures="Figures" data-metrics="Article Metrics" data-related="Related articles" data-supplementary="Supplementary materials"></template><template id="collapsible_authors_template"><button aria-expanded="false" data-expandable="all" data-label-expand="Expand All" data-label-collapse="Collapse All" class="collateral-contributors-control"><span>Expand All</span></button></template> <template id="collapsible_tables_collapse_template"><div class="collapsible-figure-btn__wrapper expanded"><button aria-expanded="true" class="btn collapsible-figure-btn btn--inverse"><i aria-hidden="true" class="icon-arrow-up"></i><span class="text-uppercase">Collapse</span></button></div></template> <template id="collapsible_tables_expand_template"><div class="collapsible-figure-btn__wrapper collapsed"><button aria-expanded="false" class="btn collapsible-figure-btn btn--inverse"><i aria-hidden="true" class="icon-arrow-down"></i><span class="text-uppercase">Expand Table</span></button></div></template><template id="authorsAffiliationsLink"><a href="#tab-contributors" class="to-authors-affiliations">Authors Info & Affiliations</a></template></div> </div> </div> </div></div> </div> </div> <div data-widget-id="606d85fd-867a-4903-8f68-000f6ab4e15f" data-widget-name="UX3HTMLWidget"><style>/* GLOBAL HEADER and SEARCH ROW: */ .ux3 .header,.ux3 .quick-search .dropBlock [data-db-target-of]::before{background:#003366 !important}.ux3 .quick-search__button::before{color:#003366 !important}.ux3 .quick-search__button:focus,.ux3 .quick-search__button:hover{opacity:.85}.ux3 .quick-search__button:focus,.ux3 .quick-search__button:hover{background:#fff!important} /* ARTICLE PAGE */ .article-header .author__search i,.article-header .author__search:hover span,.article-header .content-navigation:not(.js--sticky) a:focus i,.article-header .content-navigation:not(.js--sticky) a:hover i,.article__body h1,.article__body h2,.article__body h3,.article__body h4,.article__body h5,.article__body h6,.content-navigation__body__top,.figure-viewer__thumbslist .current .thumbnail__label,table th{color:#003366 !important}.left-side-nav li a.active,.left-side-nav li a.js--active,.left-side-nav li a:hover{color:#003366 !important;border-left-color:#003366 !important}.content-navigation.js--sticky a:focus,.content-navigation.js--sticky a:hover{background-color:#003366 !important}.article-header__info__email,.figure-viewer__close,.left-side-nav__ctrl,.upsell-box__banner{background:#003366 !important}.figure-viewer__thumbslist .current .thumbnail{border-color:#003366 !important}.article-header__overlay{background:linear-gradient(100deg,#00264d 0,#003366 50%, #003d7a 100%)!important}</style></div> <div data-widget-def="ux3-layout-widget" data-widget-id="637fb9ce-735b-43bf-a200-c13296f28a9b" class="ux3"> <div data-widget-id="637fb9ce-735b-43bf-a200-c13296f28a9b" data-widget-name="ux3-layout-widget"><div class="footer clearfix"> <div data-widget-id="c7617e63-9788-4e9b-9592-37f0c6bf7ae0" data-widget-name="UX3HTMLWidget"><div class='footer__bottom text-onDark'> <ul id='footerSiteLinks'> <li class='footerLink'> <a href='/home'>Home</a> </li> <li class='footerLink'> <a href='/developing-countries'>Access for Developing Countries</a> </li> <li class='footerHeading'>Articles & Issues</li> <li class='footerLink'> <a href='/inpress'>Articles In Press</a> </li> <li class='footerLink'> <a href='/current'>Current Issue</a> </li> <li class='footerLink'> <a href='/issues'>List of Issues</a> </li> <li class='footerHeading'>Special Issues</li> <li class='footerLink'> <a href='/issue/S1465-3249(19)X0003-1'>Evaluation of Manufactured Cellular Products</a> </li> <li class='footerLink'> <a href='/issue/S1465-3249(18)X0003-6'>ISCT 2018 Annual Meeting</a> </li> <li class='footerLink'> <a href='/issue/S1465-3249(17)X0011-X'>Cell Therapy for Infectious Diseases</a> </li> <li class='footerLink'> <a href='/issue/S1465-3249(17)X0004-2'>ISCT 2017 Annual Meeting</a> </li> <li class='footerLink'> <a href='/issue/S1465-3249(16)X0011-4'>SI: Gene Modified Cell Therapies</a> </li> <li class='footerLink'> <a href='/issue/S1465-3249(16)X0005-9'>22nd Annual ISCT Meeting</a> </li> <li class='footerLink'> <a href='/content/jcyt-special-issue-umbilical-cord-blood'>Umbilical Cord Blood: Advances and Opportunities</a> </li> <li class='footerLink'> <a href='/issue/S1465-3249(15)X0002-8'>21st ISCT Annual Meeting</a> </li> <li class='footerLink'> <a href='/issue/S1465-3249(14)X0004-6'>20th Annual ISCT Meeting</a> </li> <li class='footerLink'> <a href='/issue/S1465-3249(13)X0014-3'>19th ISCT Annual Meeting</a> </li> <li class='footerHeading'>Collections</li> <li class='footerLink'> <a href='/content/jcyt-isct-publications'>ISCT Publications</a> </li> <li class='footerLink'> <a href='/content/jcyt-talking-with-giants'>Talking with Giants</a> </li> <li class='footerHeading'>For Authors</li> <li class='footerLink'> <a href='/open-access-information'>About Open Access</a> </li> <li class='footerLink'> <a href='/authorinfo'>Author Information</a> </li> <li class='footerLink'> <a href='/content/permission'>Permissions</a> </li> <li class='footerLink'> <a href='https://researcheracademy.elsevier.com' target='_blank'>Researcher Academy</a> </li> <li class='footerLink'> <a href='https://www.editorialmanager.com/JCYT' target='_blank'>Submit a Manuscript</a> </li> <li class='footerHeading'>Journal Info</li> <li class='footerLink'> <a href='/open-access-information' >About Open Access</a> </li> <li class='footerLink'> <a href='/aims'>About the Journal</a> </li> <li class='footerLink'> <a href='/claim/activate'>Activate Online Access</a> </li> <li class='footerLink'> <a href='http://www.myhealthtalent.com' target='_blank'>Career Opportunities</a> </li> <li class='footerLink'> <a href='/contact'>Contact Information</a> </li> <li class='footerLink'> <a href='/edboard'>Editorial Board</a> </li> <li class='footerLink'> <a href='http://www.elsmediakits.com' target='_blank'>Info for Advertisers</a> </li> <li class='footerLink'> <a href='/pricing'>Pricing</a> </li> <li class='footerLink'> <a href='http://reprints.elsevier.com' target='_blank'>Reprints</a> </li> <li class='footerLink'> <a href='/user/alerts'>New Content Alerts</a> </li> <li class='footerHeading'> <a href='/pricing'>Subscribe</a> </li> <li class='footerHeading'> <a href='http://www.celltherapysociety.org'>ISCT</a> </li> <li class='footerHeading'>More Periodicals</li> <li class='footerLink'> <a href='http://www.journals.elsevierhealth.com/periodicals/home'>Find a Periodical</a> </li> <li class='footerLink'> <a href='http://www.elsevierhealth.com'>Go to Product Catalog</a> </li> </ul> </div> <style>.footer__bottom a {text-decoration: none;color: #005789;} .footer__bottom a:hover {text-decoration: underline;} ul#footerSiteLinks {column-count: 5; list-style: none; margin-top: 2em; margin-right: 20px; margin-bottom:40px;} ul#footerSiteLinks li {margin-bottom: 20px; color: #505050; text-decoration: none; font-size: 14px; } ul#footerSiteLinks li.footerHeading {text-transform: uppercase; color: #63666a; font-weight: bold; font-size: 13px;} @media screen and (max-width: 1100px) { ul#footerSiteLinks {column-count:2;}} @media screen and (max-width: 550px) { ul#footerSiteLinks {column-count:1;}}</style></div> <div class="align-center copy-right"> <div data-widget-id="0c47df72-dc53-47d6-a894-88946220b838" data-widget-name="UX3HTMLWidget"><style> button#cookieBtn { text-decoration: none; background-color: transparent; color: #005789; font-weight: bold; padding: 0; margin: 0; font-size: 14px; } button#cookieBtn:hover { text-decoration: underline; } </style> <script> // HIDE ONETRUST BACKGROUND AFTER USER PRESSES ESCAPE KEY setTimeout(function(){ $("#onetrust-pc-sdk").on("keydown", function(e) { if (e.keyCode == 27) { // ESC key setTimeout(function(){ $(".onetrust-pc-dark-filter").css("display","none"); }, 100); } }); }, 5000); </script> <hr/> <p align="center"><b>The content on this site is intended for healthcare professionals.</b></p> <hr/><br/> <div class="es-footer-cookie"> We use cookies to help provide and enhance our service and tailor content. To update your cookie settings, please visit the <b><button id="cookieBtn" class="ot-sdk-show-settings" type="button" aria-label="Manage cookie consent preferences">Cookie Settings</button></b> for this site.<br /> </div>  All content on this site: Copyright © 2024 Elsevier Inc., its licensors, and contributors. <br/>All rights are reserved, including those for text and data mining, AI training, and similar technologies. <br/>For all open access content, the relevant licensing terms apply. <br /><br /> <ul class="rlist--inline"> <li><a href="https://www.elsevier.com/legal/privacy-policy" target="_blank">Privacy Policy</a>  </li> <li><a href="https://www.elsevier.com/legal/elsevier-website-terms-and-conditions" target="_blank">Terms and Conditions</a>  </li> <li><a href="https://www.healthadvance.com/accessibility" target="_blank">Accessibility</a>  </li> <li><a href="https://service.elsevier.com/app/overview/healthadvance/" target="_blank">Help & Contact</a></li> </ul> <br> <a href="https://www.relx.com"><img src="/pb/assets/raw/Health%20Advance/images/relx-1554393210983.png" alt="RELX" rel="nofollow" target="_new"></a> <br> <br></div> </div> <div data-widget-id="50c9dc39-d4fb-48f7-9891-1192d9d27bd3" data-widget-name="UX3HTMLWidget"><style> .ux3 .admin-tool-bar input{ width: 15%; padding: 0; } .ux3 .admin-tool-bar [type=button]{ padding: 5px; } .ux3 .footer .copy-right{ padding: 0; } </style></div> <div data-widget-id="3c9b021b-bfb2-4fcd-9711-c919a04ed2a6" data-widget-name="UX3HTMLWidget"><style> /*This was added temporarily until the PB changelog tab issue got fixed. [LIT-444969 - c#4]*/ [data-tab-id="changelogTab"] { display: none !important; } /*This was added temporarily until the PB changelog tab issue got fixed. [LIT-518839]*/ @media (min-width: 769px) { .ux3 .quick-search .dropBlock [data-db-target-of], .quick-search .dropBlock [data-db-target-of] { width: 100vw !important; } } </style></div> </div></div> </div> <div data-widget-id="77cf9626-56c1-43c4-965f-6c77d9b11e9d" data-widget-name="UX3HTMLWidget"></div> <div data-widget-id="e4d792f7-1093-41b0-98c0-eba3790b8462" data-widget-name="UX3HTMLWidget"> <style> .journal-logos:nth-of-type(2) img { max-height: 45px !important; } .journal-logos:nth-of-type(3) img { max-height: 45px !important; } .ux3 .journal-logos + .journal-logos { margin-left: 24px; } .header__wrapper.clearfix .col-xs-6:first-of-type { width: 55%; } .header__wrapper.clearfix .col-xs-6:nth-of-type(2) { width: 45%; } @media screen and (max-width: 1000px) { .ux3 .journal-logos + .journal-logos { display: none; } .header__wrapper.clearfix .col-xs-6:first-of-type { width: 50%; } .header__wrapper.clearfix .col-xs-6:nth-of-type(2) { width: 50%; } } </style></div> <div class="widget sessionValidationWidget none widget-none" id="454875d4-cdd3-43d7-8792-9ad9208efb7a"> <div class="wrapped " > <div class="widget-body body body-none "><script> $.ajax({ url: "https://www.isct-cytotherapy.org/ssoSessionCheck", type: "GET", dataType: "jsonp", success: function (data) { if(data.RefreshSession) { location.reload(); } }, error : function (){ console.warn("can't validate CSAS session."); } }); </script></div> </div> </div> <div class="widget csasSsoUrls none widget-none" id="50d01d29-5810-433b-8bff-c2b88479f2e2"> <div class="wrapped " > <div class="widget-body body body-none "> <script> setTimeout(clearSsoUrlsFun,10000); var iFramesList = document.getElementById("sso-urls-div").getElementsByTagName("iframe"); var renderedIFramesCount = 0; var numberOfIFrames = iFramesList.length; var skipRefresh = false; for (var i = 0; i < iFramesList.length; i++) { var iFrame = iFramesList[i]; iFrame.addEventListener("load", function() { renderedIFramesCount = renderedIFramesCount + 1; if (renderedIFramesCount >= numberOfIFrames) { clearSsoUrlsFun(); } }); } function clearSsoUrlsFun() { if (skipRefresh == false && numberOfIFrames > 0) { skipRefresh = true; $.ajax({ url: "https://www.isct-cytotherapy.org/action/clearSsoUrls", type: "GET", dataType: "jsonp", error : errorCallingAjx }); } } function errorCallingAjx(){ console.log("can't delete sso urls .") } </script></div> </div> </div> <div data-widget-id="fa8d412e-f343-42d1-87dd-a0d7c0e17943" data-widget-name="UX3HTMLWidget"> <script> // open society logos in new window $(document).ready(function() { $(".journal-logos:nth-of-type(2) a").attr("target","_blank"); }); </script></div> <div class="widget general-html-asset none noMargin widget-none widget-compact-all" id="1b790202-7372-444f-9ad5-bd3893faa6a3"> <div class="wrapped " id='NAV BAR STYLES'> <div class="widget-body body body-none body-compact-all"><style> /* Article List */ .navarticlecss h4.meta__title { text-decoration:none!important; font-size:14px!important; line-height:19px!important; margin-bottom:0px!important; margin-top:0px!important; } .navarticlecss .meta__header { display:none; } .navarticlecss .OALabel { display:none!important; } /* .navarticlecss .search__item__body { padding-bottom:18px!important; } */ .navarticlecss .search__item { border:0px!important; padding:0px!important; background-color:transparent!important; } .listDropZone h2 { font-size:1rem!important; margin-top:0px!important; border-bottom:.0625rem solid #bdbdbd; padding: 0 0 .3125rem!important; margin-bottom:.625rem!important; font-weight:400; } .navarticlecss .publication-list .search__item { margin:0 0 0.5rem!important; } /* News DO */ .navdocss .search-result__toolbar-bottom { display:none; } .navdocss .do-date { display:none; } .navdocss .do-breadcrumb { display:none; } .navdocss .search-result__count { display:none; } .navdocss .do-search-result-cards.search-result__body { margin-top: 0px!important; } .navdocss .do-item-description { display:none; } /* Nav Video DO */ .navvideodocss .do-item-media--video { display:none; } .navvideodocss .do-item-content { padding:0px!important; } .navvideodocss .do-media-links { display:none!important; } .navvideodocss .do-item-content h3 { line-height:1.4rem!important; font-size:14px!important; } .navvideodocss .do-card{ border:0px!important; background-color:transparent; } /* Nav CfP */ .navcfpdo .do-item-content .do-item-description { display:none; } .navcfpdo .do-breadcrumb { display:none; } .navcfpdo .do-list-item .do-date { display:none; } .navcfpdo .do-item-content h3 { font-size: 14px!important; } .navcfpdo .search__item { border-bottom: 0px!important; } .navcfpdo .items-results--articles .search__item { padding:0px!important; margin-bottom:7px; } </style><script defer src="https://static.cloudflareinsights.com/beacon.min.js/v52afc6f149f6479b8c77fa569edb01181681764108816" integrity="sha512-jGCTpDpBAYDGNYR5ztKt4BQPGef1P0giN6ZGVUi835kFF88FOmmn8jBQWNgrNd8g/Yu421NdgWhwQoaOPFflDw==" data-cf-beacon='{"rayId":"7d4ab435ba3129e4","token":"57a02315956f4b2e82817b3dfa99b1a2","version":"2023.4.0","si":100}' crossorigin="anonymous"></script></div> </div> </div> <div data-widget-id="01ea3c0a-522b-45b3-a8ae-409a6e2b6711" data-widget-name="UX3HTMLWidget"><style> .stickied div.inner-wrapper { z-index: 0; } </style> <script> // move Download Full Issue button $(".core-header-aside .article-header__download-full-issue").detach().appendTo("header .meta-panel"); // hide the Download Full Issue popup $(".meta-panel > div:not(:empty) > div").css("display","none"); // add CSS - mostly spacing $("body").append("<style>.meta-panel__right {margin-right: 20px;} @media (max-width: 1179px) {.meta-panel .meta-panel__right {display: block;} .meta-panel .meta-panel__right + .article-header__download-full-issue button.btn--download-issue {margin-top: 9px; min-height: 32px !important;} .article-header__download-full-issue .download-full-issue > span {font-size: 14px;}} .article-header__download-full-issue .download-full-issue:focus, .article-header__download-full-issue .download-full-issue:hover {background-color: #727272;}</style>"); </script></div> </div> </div> <script src="/products/marlin/ha/releasedAssets/js/main.bundle-93f7882900b3a917b004.js"></script> <script type="text/javascript"> var pageData = {"journal":{"specialty":"Hematology,Oncology","issn":"1465-3249","name":"Cytotherapy"},"page":{"loadTimestamp":"1732714880081","server":"healthadvance.com","environment":"prod","businessUnit":"ELS:RAP:JBS","noTracking":"","name":"fulltext:html","section":"Other journal branded sites","language":"en","type":"CP-CA","productName":"JB"},"visitor":{"departmentName":"ae:Journal Branded Solutions - Guests|ae:ScienceDirect Guests","accessType":"ae:ANON_GUEST|ae:ANON_GUEST","accountId":"ae:375335|ae:228598","accountName":"ae:Journal Branded Solutions - Guests|ae:ScienceDirect Guests","departmentId":"ae:388406|ae:291352","ipAddress":"8.222.208.146","loginStatus":"anonymous","userId":"ae:19319093|ae:12975512"},"content":[{"accessType":"article:free:openaccess","volumeNumber":"25","issueNumber":"9","viewState":"fulltext","format":"MIME-HTML","id":"pii:S1465324923000646","coverDate":"202309","type":"XOCS-JOURNAL:SCOPE-FULL","title":"International Society for Cell amp Gene Therapy Position Paper Key considerations to support evidencebased cell and gene therapies and oppose marketing of unproven products","status":"S300"}]}; </script> <script type="text/javascript"> if(typeof pageDataTracker !== "undefined") { pageDataTracker.trackPageLoad(); } </script> </body> </html>

CINXE.COM

International Society for Cell & Gene Therapy Position Paper: Key considerations to support evidence-based cell and gene therapies and oppose marketing of unproven products - Cytotherapy