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dcrname ="iwDCR0_111247"> <header class="-padding--horizontal" itemscope itemtype="http://schema.org/ScholarlyArticle"> <div class="content-header content-container -width--wide -centered"> <div class="tags"> <ul class="tag__list"> <li class="tag__item"> <a class="tag__link" href="/research-and-innovation/topic.aspx?id=1114">Gene and Cell Therapy</a> </li> <li class="tag__item"> <a class="tag__link" href="/neuro/topic.aspx?id=1018">Neurology</a> </li> <li class="tag__item"> <a class="tag__link" href="/neuro/specialty.aspx?id=1004">Neuroscience</a> </li> <li class="tag__item"> <a class="tag__link" href="/neuro/topic.aspx?id=1019">Neurosurgery</a> </li> <li class="tag__item"> <a class="tag__link" href="/neuro/topic.aspx?id=1055">Parkinson's Disease</a> </li> <li class="tag__item"> <a class="tag__link" href="/research-and-innovation/topic.aspx?id=1079">Stem Cell Therapy</a> </li> </ul> </div> <h1 class="content-header__heading" itemprop="name">Co-transplantation of Regulatory T Cells Improves Cell Replacement Therapy for Parkinson's Disease</h1> <div class="content-header__metadata"> <p class="content-metadata"> <span class="content-metadata__media -journal">Journal</span> <time class="date" datetime="2023-09-19" itemprop="datePublished">Published on September 19, 2023 </time> </p> <p data-module="share-links"> </p> <p class="citation"> Originally published on <cite itemprop="citation"><a href="https://www.nature.com/articles/s41586-023-06300-4">Nature</a></cite> </p> </div> </div> </header> <div class="-padding--vertical -padding--horizontal"> <div class="layout-columns -width--wide -centered"> <div class="layout-columns__main"> <div class="layout-columns__main__content"> <div class="content-summary"> <h3 class="content-summary__heading">Key findings</h3> <ul> <li>Transplantation of autologously derived dopamine neurons has shown promise in both pre-clinical and clinical studies for the treatment of Parkinson's disease, but survival of the cells has been poor</li> <li>This study examined how the immediate reaction of host brain tissue to the surgical injury of transplantation affects the survival of the therapeutic tyrosine hydroxylase (TH)<sup>+</sup> dopamine neurons within the graft</li> <li>In rodent models of autologous dopamine neuron transplantation, the penetrating trauma of surgical implantation induced an immediate host inflammatory response, termed needle trauma, that substantially harmed the TH<sup>+</sup> cells that are key to the success of the therapy, but not TH<sup>-</sup> cells</li> <li>Regulatory T (T<sub>reg</sub>) cells derived from the host mitigated the needle trauma–induced harm to the dopaminergic cells in both autologous and xenogeneic grafts, leading to better improvement of motor deficits in this rat model of Parkinson's disease</li> <li>Co-transplantation of a patient's T<sub>reg</sub> cells could improve clinical outcomes of cell therapy after both autologous and allogeneic cell transplantation</li> </ul> </div> <p>The motor symptoms of Parkinson's disease (PD) correlate with selective, progressive degeneration of midbrain dopamine neurons. Transplantation of autologously derived dopamine neurons, that is, created from the patient's own cells, has shown promise in a recent clinical study, but survival of the cells has been poor.</p><div class="article__signup-container"> <div class="email-signup-inline__container -background--white"> <style> #email-signup-inline { /* 540px */ background-image: url(/assets/raw/email-signup/cardiovascular-sub-callout.jpg); } @media only screen and (-webkit-min-device-pixel-ratio: 2), only screen and (min--moz-device-pixel-ratio: 2), only screen and (-moz-min-device-pixel-ratio: 2), only screen and (-o-min-device-pixel-ratio: 2/1), only screen and (min-device-pixel-ratio: 2), only screen and (min-resolution: 192dpi), only screen and (min-resolution: 2dppx) { #email-signup-inline { /* 1080 width */ background-image: url(/assets/raw/email-signup/cardiovascular-sub-callout.jpg); } } </style> <div class="content-container -width--wide -centered email-signup-inline__wrapper" id="email-signup-inline"> <div class="email-signup-inline__logo"> <img alt="Massachusetts General Hospital " src="/assets/logos/logo-white.svg"> </div> </div> <div class="email-signup-inline"> <h3 class="email-signup-inline__heading">Subscribe to the latest updates from Neuroscience Advances in Motion</h3> <p class="email-signup-inline__subheading"></p>  <meta http-equiv="Content-Type" content="text/html; 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</script> <script type="text/javascript" src="https://massgeneral.tfaforms.net/wForms/3.11/js/localization-en_US.js?v=20484c23150f9374e828ae7e95c879908749f33b"></script>  <div class="wFormContainer" > <div class=""><div class="wForm" id="527-WRPR" data-language="en_US" dir="ltr"> <div class="codesection" id="code-527"></div> <form method="post" action="https://massgeneral.tfaforms.net/api_v2/workflow/processor" class="hintsBelow labelsAbove" id="527"> <div class="oneField field-container-D " id="tfa_9-D"> <div aria-live="assertive"> <p class="marketo-signup__error"> Error: Please enter a valid email address. </p> </div> <p class="marketo-signup__input" data-module="label-float"> <label for="email-address"> Email Address </label> <input type="email" id="tfa_9" name="tfa_9" value="" data-marketo="email" > <button class="fat-button" type="submit" data-label="Submit" class="primaryAction" id="submit_button" value="Submit"> <span class="a11y-sr-only">Submit</span> </button> </p> <input type="hidden" id="tfa_10" name="tfa_10" value="Sub_Neuro" class=""><input type="hidden" id="tfa_12" name="tfa_12" value="AiM Sub Box" class=""> </div> <div style="clear:both"></div> <input type="hidden" value="527" name="tfa_dbFormId" id="tfa_dbFormId"> <input type="hidden" value="" name="tfa_dbResponseId" id="tfa_dbResponseId"> <input type="hidden" value="c74f0ac873f725872c9b5d8effcbf21d" name="tfa_dbControl" id="tfa_dbControl"> <input type="hidden" value="" name="tfa_dbWorkflowSessionUuid" id="tfa_dbWorkflowSessionUuid"> <input type="hidden" value="4" name="tfa_dbVersionId" id="tfa_dbVersionId"> <input type="hidden" value="" name="tfa_switchedoff" id="tfa_switchedoff"> </form> </div> </div> </div> <script id="open-telemetry-script" type="text/javascript" src="https://massgeneral.tfaforms.net/dist/open-telemetry/open-telemetry.152f594b0ae29ae89d4a.js" data-customer-id="1118" data-exporter-url="https://us-east-1-otel.formassembly.com/v1/traces" data-exporter-console="0" ></script> <script src="https://massgeneral.tfaforms.net/api_v2/sst/copy-and-paste"></script> </div> </div> </div> <p>Researchers at Massachusetts General Hospital previously reported in<span> </span><a title="Patient-derived Dopamine Neurons Show Promise in Parkinson's Treatment" href="https://advances.massgeneral.org/neuro/article.aspx?id=1200" target="_blank" rel="noopener noreferrer"><em>NEJM</em></a><span> </span>the successful transplantation of midbrain dopaminergic progenitor cells, differentiated<span> </span><em>in vitro</em><span> </span>from autologous induced pluripotent stem (iPS) cells, into a patient with PD without using immunosuppressants. However, functional recovery was only modest, suggesting cell survival was still limited.</p> <p>Now, the group has determined an important reason why most grafted therapeutic neurons die and identified a method to substantially improve their survival.<span> </span><a title="Research contributions by Todd M. Herrington, MD, PhD" href="https://advances.massgeneral.org/contributors/contributor.aspx?id=1641">Todd M. Herrington, MD, PhD</a>, director of Mass General's<span> </span><a title="The Deep Brain Stimulation Program at Mass General" href="https://www.massgeneral.org/neurology/xdp-center/patients/deep-brain-stimulation">Deep Brain Stimulation Program</a>,<span> </span><a title="Research contributions by Bob S. Carter, MD, PhD" href="https://advances.massgeneral.org/contributors/contributor.aspx?id=1106">Bob S. Carter, MD, PhD</a>, chief of the<span> </span><a title="The Department of Neurosurgery at Mass General" href="https://www.massgeneral.org/neurosurgery/">Department of Neurosurgery</a>,<span> </span><a title="Research contributions by Jeffrey S. Schweitzer, MD, PhD" href="https://advances.massgeneral.org/contributors/contributor.aspx?id=1112">Jeffrey S. Schweitzer, MD, PhD</a>, neurosurgeon,<span> </span><a title="Kwang-Soo Kim, PhD, Profile" href="https://www.mcleanhospital.org/profile/kwang-soo-kim" target="_blank" rel="noopener noreferrer">Kwang-Soo Kim, PhD</a>, director of the Molecular Neurobiology Laboratory at<span> </span><a title="Neuroscience Research at McLean Hospital" href="https://www.mcleanhospital.org/research/neuroscience" target="_blank" rel="noopener noreferrer">McLean Hospital</a>, and colleagues detail their findings in<span> </span><a title="Co-transplantation of autologous Treg cells in a cell therapy for Parkinson’s disease" href="https://www.nature.com/articles/s41586-023-06300-4" target="_blank" rel="noopener noreferrer"><em>Nature</em></a><em>.</em></p> <h2>Rapid Loss of Therapeutic Cells After Transplantation</h2> <p>The researchers first transplanted iPS cell–derived midbrain dopamine progenitor cells from a patient with PD into mice humanized with immune cells autologous to the patient. They discovered the penetrating trauma of surgical implantation, which they term needle trauma, induced a host inflammatory response that harmed the therapeutic tyrosine hydroxylase (TH)<sup>+</sup><span> </span>cell portion of the graft. More than 90% of TH<sup>+</sup><span> </span>cells died within two weeks.</p> <p>In contrast, TH<sup>−</sup><span> </span>cells mostly survived whether they were transplanted into immunodeficient or immunocompetent host animals, including humanized mice. These findings were validated independently in human cell lines.</p> <h2>Effects of T<sub>reg </sub>Cells</h2> <p><em>In vitro,</em><span> </span>TH<sup>+</sup><span> </span>neurons were significantly rescued by co-incubation with autologous regulatory T cells. The team, therefore, decided to try co-transplanting autologous regulatory T (T<sub>reg)</sub><span> </span>cells during surgical implantation of neurons, hoping to suppress the host inflammatory response to needle trauma.</p> <p>In autologous and xenogeneic grafts in rodent models of PD, that strategy significantly protected both host neurons and grafted midbrain dopamine neurons from needle trauma–induced death and improved behavioral recovery.</p> <p>This suggests that while using an autologous cell source can avoid the need for immunosuppression to blunt the host's adaptive immune response, i.e., tissue rejection, there is still a significant attack on the graft related to the innate immune response triggered by the needle trauma.</p> <p>Unexpectedly, co-transplantation of T<sub>reg</sub><span> </span>cells substantially reduced the expansion of the grafts related to TH<sup>−</sup><span> </span>cells, resulting in a significantly smaller graft volume with a higher proportionate TH<sup>+</sup><span> </span>cell content and improved outgrowth from the grafts.</p> <p>The T<sub>reg</sub><span> </span>cells themselves did not persist in long-term grafts (assessed at six months), suggesting the benefits are related to modulation of the acute innate immune response and subsequent administration of the cells would not be required. The strategy should thus reduce a patient's time at risk of adverse effects and the extent of that risk.</p><p class="fat-link__wrapper u-text-right"> <a class="fat-link -caret -large" href="https://www.nature.com/articles/s41586-023-06300-4">view original journal article <em>Subscription may be required</em></a> </p> <div class="article-attribution" itemscope itemtype="http://schema.org/ScholarlyArticle"> <p class="article-attribution__logo" itemscope itemtype="http://schema.org/Periodical"> <a href="https://www.nature.com/articles/s41586-023-06300-4"> <span class="a11y-sr-only" itemprop="name">Nature</span> </a> </p> <p class="article-attribution__metadata" itemscope itemtype="http://schema.org/PublicationIssue"> <span> Journal Article Published: <time datetime="2023-07-12" itemprop="datePublished">July 12, 2023</time> </span> </p> </div> <p class="cta">Learn more about the <a href="https://www.massgeneral.org/neurosurgery">Department of Neurosurgery</a></p> <p class="cta">Refer a patient to the <a href="https://www.massgeneral.org/neurosurgery/appointments-and-referrals">Department of Neurosurgery</a></p> </div> </div> <aside class="layout-columns__sidebar -article__contributors"> <div class="layout-columns__sidebar__content"> <div class="profile-compact__wrapper"> <p class="u-no-margin"> <strong>Contributors</strong> </p> <div class="profile -compact" itemscope itemtype="http://schema.org/Person"> <div class="profile__content"> <h3 class="profile__name" itemprop="name"> <a href="/contributors/contributor.aspx?id=1106" itemprop="url">Bob S. Carter, MD, PhD ›</a></h3><p class="profile__title" itemprop="jobTitle">Chief, Neurosurgery Service</p> </div> <p class="profile__image"> <img alt="" itemprop="image" srcset="/assets/images/contributors/Bob_Carter_20120_advances.png, /assets/images/contributors/Bob_Carter_20120_advances_2x.png 2x" src="/assets/images/contributors/Bob_Carter_20120_advances.png"> </p> </div> <div class="profile -compact" itemscope itemtype="http://schema.org/Person"> <div class="profile__content"> <h3 class="profile__name" itemprop="name"> <a href="/contributors/contributor.aspx?id=1112" itemprop="url">Jeffrey S. Schweitzer, MD, PhD ›</a></h3><p class="profile__title" itemprop="jobTitle">Neurosurgeon, Department of Neurosurgery, Massachusetts General Hospital, Assistant Professor of Neurosurgery, Harvard Medical School</p> </div> <p class="profile__image"> <img alt="Jeffrey Schweitzer, MD, PhD" itemprop="image" srcset="/assets/images/contributors/Jeffrey_Schweitzer_20345_advances.png, /assets/images/contributors/Jeffrey_Schweitzer_20345_advances_2x.png 2x" src="/assets/images/contributors/Jeffrey_Schweitzer_20345_advances.png"> </p> </div> <div class="profile -compact" itemscope itemtype="http://schema.org/Person"> <div class="profile__content"> <h3 class="profile__name" itemprop="name"> <a href="/contributors/contributor.aspx?id=1641" itemprop="url">Todd M. Herrington, MD, PhD ›</a></h3><p class="profile__title" itemprop="jobTitle">Director, Deep Brain Stimulation Program, Massachusetts General Hospital</p> </div> <p class="profile__image"> <img alt="" itemprop="image" srcset="/assets/images/contributors/todd_harrington_advances.png, /assets/images/contributors/todd_harrington_advances_2x.png 2x" src="/assets/images/contributors/todd_harrington_advances.png"> </p> </div> </div> </div> </aside> <section class="topics-layout -article__related"> <div class="topics-layout__inner"> <div class="topics-layout__sidebar"> <h2 class="section-heading">Related topics</h2> </div> <div class="topics-layout__main"> <ul class="topics-list" data-module="topics-list"> <li><a href="/research-and-innovation/topic.aspx?id=1114">Gene and Cell Therapy</a></li> <li><a href="/neuro/topic.aspx?id=1018">Neurology</a></li> <li><a href="/neuro/topic.aspx?id=1019">Neurosurgery</a></li> <li><a href="/neuro/topic.aspx?id=1055">Parkinson's Disease</a></li> <li><a href="/research-and-innovation/topic.aspx?id=1079">Stem Cell Therapy</a></li> </ul> </div> </div> </section> <section class="-padding--horizontal -padding--vertical -article__related"> <div class="layout-columns -width--wide -centered"> <div class="layout-columns__pod--half"> <div class="content-tease" itemscope itemtype="http://schema.org/ScholarlyArticle"> <p class="content-tease__topic"> <span class="highlight">Related</span> </p> <h3 class="content-tease__heading" itemprop="name"> <a href="/neuro/article.aspx?id=1200" itemprop="url">Patient-derived Dopamine Neurons Show Promise in Parkinson's Treatment</a> </h3> <p itemprop="description"> <p></p> <p>Massachusetts General Hospital and McClean Hospital researchers take significant steps towards proving the safety and efficacy of dopaminergic neuron implantation to treat Parkinson's disease.</p> <p></p> <p></p> <p></p> <p></p> <p></p> <p></p> <p></p> <p></p> <p></p></p> <p class="content-tease__related"> <a 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href="/neuro/journal.aspx?id=1551" itemprop="url">First-In-Human Therapy with Stem Cell–derived Dopaminergic Progenitor Cells for Parkinson's Disease</a> </h3> <p itemprop="description"> <p></p> <p></p> <p></p> <p>Mass General researchers report substantial clinical improvement in a patient with Parkinson's disease after they implanted midbrain dopaminergic progenitor cells that they differentiated in vitro from autologous induced pluripotent stem cells.</p> <p></p> <p></p> <p></p> <p></p> <p></p> <p></p> <p></p> <p></p> <p></p> <p></p> <p></p> <p></p> <p></p> <p></p> <p></p> <p></p> <p></p></p> <p class="content-tease__related"> <a href="/research-and-innovation/topic.aspx?id=1114" itemprop="relatedLink">Gene and Cell Therapy</a>, <a href="/neuro/topic.aspx?id=1024" itemprop="relatedLink">Neurodegenerative Disease</a>, <a href="/neuro/topic.aspx?id=1018" itemprop="relatedLink">Neurology</a>, <a href="/neuro/specialty.aspx?id=1004" itemprop="relatedLink">Neuroscience</a>, <a 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