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Human Plasma-Like Medium | Thermo Fisher Scientific - SG

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468bd07150dbbf Source: /tf/js/dist/digitaldata.js */ (function () { "use strict"; /** * Invoking a Function as a Method * define function as object methods * @type {Object} */ window.digitalData = { user: {}, page: {}, merchandising: {}, getQueryParam : function (param) { var index, key, value, hash; var hashes = window.location.href.slice(window.location.href.indexOf('?') + 1).split('&'); for (index = 0; index < hashes.length; index++) { hash = hashes[index].split('='); key = hash[0]; value = hash[1]; if (key.toUpperCase() === param.toUpperCase()) return value; } return ''; }, getValOnce: function (value, cookieName, expiry, timeUnit) { var currentDate = new Date; var currentCookieValue; // timeUnit of 'm' is minutes represented in milliseconds // thus 86400000 = 24 hours = 1 day var interval = timeUnit == 'm' ? 60000 : 86400000; cookieName = cookieName ? cookieName : 'digitaldata_gvo'; value = value ? value : ''; expiry = expiry ? expiry : 0; currentCookieValue = this.getCookie(cookieName); if (value) { currentDate.setTime(currentDate.getTime() + expiry * interval); this.setCookie(cookieName, value, expiry == 0 ? 0 : currentDate); } return value == currentCookieValue ? '' : value; }, getCookie: function (key) { var result = ""; var cookies = document.cookie ? document.cookie.split('; ') : []; for (var i = 0; i < cookies.length; i++) { var parts = cookies[i].split('='); var name = decodeURIComponent(parts.shift()); var cookie = parts ? parts.join('=') : []; // Prevent storing or parsing of a cookie that we couldn't decode. if (cookie && key === name) { // removes surrounding quotes if (cookie.indexOf('"') === 0) { // This is a quoted cookie as according to RFC2068, unescape... cookie = cookie.slice(1, -1).replace(/\\"/g, '"').replace(/\\\\/g, '\\'); } // parse utf8 characters try { cookie = decodeURIComponent(cookie); } catch (e) {} result = cookie; // we found it, don't bother looking at other cookies break; } } return result; }, setCookie : function(name, value, numDays){ if ( !numDays ) numDays = 31; var expires = new Date(); expires.setTime(expires.getTime() + (1000 * 60 * 60 * 24 * numDays)); document.cookie = name+ '=' + escape(value) + '; path=/; expires=' + expires.toGMTString() + '; domain=.' + this.getMasterDomain() + ';'; }, /** * get the master domain based on business rules */ getMasterDomain : function () { // default the master domain var masterDomain = 'thermofisher.com'; // check for alternate domain portion of URL var regexMatch = document.location.hostname.match(/\.(thermofisher)\.(cn)/i); if (regexMatch !== null) { masterDomain = regexMatch[1] + '.' + regexMatch[2]; } return masterDomain; }, /** * Check if init has been initiated once * @type {Boolean} */ initted: false, /** * @return {Array} method returns an array of a given object's key properties */ init: function () { this.page.country = this.getCookie("CK_ISO_CODE") || 'us'; this.page.language = this.getCookie('CK_LANG_CODE') || 'en'; this.page.siteName = 'thermo'; //hard coded this.initMerchandisingData(); this.initUserData(); this.displayDigitalData(); this.formSubmitEvent(); }, //specific function to set type of the page // need specific function to keep page type separate from other page attributes setPageType: function (type) { this.setPageAttribute('type', type); }, // generic function to set page attributes setPageAttribute: function (key, value) { this.page[key] = value; }, // display digitalData object displayDigitalData: function () { }, // specific function to add an object to digitalData addDigitDataObject: function (key, object) { this[key] = object; }, addChildObjectAttribute: function(child, key, value){ this[child][key] = value; }, initUserData: function(){ var gigyaCookie = this.getCookie("identity_uid"); this.user.gigyaId = ""; this.user.loginStatus = "anonymous"; if( gigyaCookie != ""){ this.user.gigyaId = gigyaCookie; this.user.loginStatus = "logged in"; } }, /** * Check if init has been initiated once * @type {Boolean} */ merchandisingDataInitted: false, initMerchandisingData: function () { // read cid and icid value from session cookie this.merchandising.icid = this.getCookie('s_ev21_tc'); this.merchandising.cid = this.getCookie('s_cmp_tc'); // EMID value this.merchandising.emid = this.getQueryParam("emid"); // referrer by domain if (typeof document.referrer !== 'undefined' && document.referrer.length > 0) { var masterDomain = this.getMasterDomain(); var refReg = document.referrer; var referrerDomain = refReg.match(/:\/\/([^/]+)\//); if (referrerDomain !== null && referrerDomain[1].indexOf(masterDomain) == -1) { this.merchandising.referrer = referrerDomain; } } document.addEventListener('registerMerchandisingData', function (event) { for (var key in event.detail) { console.log("Listener data copied", key, event.detail[key] ); digitalData.merchandising[key] = event.detail[key]; } // Map some analytics attributes to merchandising session attributes digitalData.merchandising.sessionId = digitalData.merchandising.analyticsVisitorID; digitalData.merchandising.s_vi_low = digitalData.merchandising.analyticsVisitorIDLow; digitalData.merchandising.s_vi_high = digitalData.merchandising.analyticsVisitorIDHigh; console.log("digitalData: Captured registerMerchandisingData event"); digitalData.merchandisingDataInitted = true; // Call emailCampaignRecord if the digitalDataAnalyticsListener object is loaded if (typeof digitalDataAnalyticsListener != "undefined") { console.log("digitalData: Calling email campaign record"); digitalDataAnalyticsListener.emailCampaignRecord(); } }); }, formSubmitEvent: function () { var formId = this.getQueryParam("form-submit-id"); if ((formId) && formId !== "" && formId !== null) { var eventDetail = { detail: { form: { id: formId } } }; var formSubmitEvent = new CustomEvent('formSubmit', eventDetail); console.log('form submit event started'); document.dispatchEvent(formSubmitEvent); console.log('form submit event fired', eventDetail); //flush grepToken from Session Storage sessionStorage.removeItem('grepTokenSO'); } }, modalVideoEvent: function (videoId) { if (((videoId) && videoId !== "" && videoId !== null)) { var eventDetail = { detail: { video: { playerId: videoId } } }; var modalVideoEvent = new CustomEvent('videoPlayerLoaded', eventDetail); document.dispatchEvent(modalVideoEvent); } }, customClickEvent: function (clickDetail) { if (((clickDetail) && clickDetail !== "" && clickDetail !== null)) { var eventDetail = { detail: { CustomLink: { linkName: clickDetail } } } var customClickEvent = new CustomEvent('customLinkClicks', eventDetail); document.dispatchEvent(customClickEvent); } } } })(); window.digitalData.init(); </script> <!-- performance-begin --> <script type="text/javascript"> window.performance && window.performance.mark && window.performance.mark("header_25"); </script> <script type="text/javascript"> var localizedStrings = { "ACCEPTANCE": "Acceptance of Terms of Use", "BTN_AGREE": "Agree", "BTN_DISAGREE": "Disagree", "PROCESSING_MESSAGE" :"processing ... please wait ...", "ADD_TO_CART_QUANTITY_ERROR":"You must provide a quantity to add an item to the cart", "ADD_TO_CART_VALID_QUANTITY_ERROR":"You must provide a valid quantity to add an item to the cart", "VIEW_CART" :"View cart &amp; checkout", "VIEW_CONTACT_DETAIL" :"View Contact Details", "ADD_TO_CART_NOTIFICATION":"Add to Cart Notification", "UPDATE_CART" :"Update Cart", "PRINCIPAL_INVESTIGATOR":"Principal Investigator", "PRINCIPAL_INVESTIGATOR_TEAM_LEADER":"Principal Investigator or Team Leader", "PRINCIPAL_INVESTIGATOR_CHIEF":"Principal Investigator or Chief", "EMAIL_ERROR_1" :"Please Provide Collegues Email", "EMAIL_ERROR_2" :"Please enter a valid colleague email address", "EMAIL_ERROR_3" :"Please Provide Your Email", "EMAIL_ERROR_4" :"Please enter a valid email address", "ERROR_OCCURED_MESSAGE" :"The following errors occured", "NEXT" :"Next", "PREVIOUS" :"Prev", "IMAGE" :"Image", "SAVE_TO_LIST_ERROR_1" :"Please enter a list name.", "SAVE_TO_LIST_ERROR_2" :"Please enter a different list name that does not include the following: ?,/,\\,%,^,!", "MINICART_ERROR_1" :"Unable to connect to eCommerce system. 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Please try again later.", "MINICART_MESSAGE_1" :"Adding item(s) to cart...", "MINICART_MESSAGE_2" :"Removing item(s) from cart...", "MINICART_CART_NAME_LABEL_1" :"Recently added to the", "MINICART_NOTE_1" : "Your total price and product details can be viewed in the cart.", MINICART_SUMMARY : "Cart summary", MINICART_PRICE : "Price", MINICART_PRODUCT : "Product", LIST_PRICE : "Price", YOUR_PRICE : "Your price", WEB_PRICE: "Online offer", PRICE_ENDS: "ends", SIGN_IN: "Sign in", //New mini cart CATALOG_NUMBER: "Catalog number:", CONTACT_US: "Contact us", RFQ: "Request quote", LEARN_WHERE_TO_BUY: "Learn where to buy", CURRENCY: "USD", //End new mini cart "CHANGE_CART" :"Change cart", "VIEW_ALL" :"View All", "ITEM" :"item", "ITEMS" :"items", "CLOSE" :"Close", "SUBTOTAL" :"Subtotal", "TOTAL" :"Total", "MANAGE_CART" :"Manage Cart", "FIELD" :"field", "GLOBAL_ERROR_1" :"Please choose one or both of the options for", "GLOBAL_ERROR_2" :"is not a valid e-mail address.", "GLOBAL_ERROR_3" :"Unsupported character(s) were found in field", "GLOBAL_ERROR_4" :"and will be replaced with plain text equivalents (where available). 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aem-GridColumn--offset--default--0"> <div id="container-f4d5a445e4" class="cmp-container"> <div class="cmp-p-container p-l1"> <div id="container-43216b0db9" class="cmp-container"> <div class="cmp-p-text mt-l1"> <div id="text-828643573" class="cmp-text"> <h2>Create physiologically relevant cell culture models with HPLM</h2> <p> </p> <p>Gibco Human Plasma-like Medium (HPLM) is formulated to resemble the natural cellular environment found in the body, mimicking the metabolic profile of human plasma. </p> <p> </p> <p>Widely used, synthetic cell culture media, including MEM, DMEM, RPMI 1640, and DMEM/F-12 contain glucose, amino acids, vitamins, and salts at concentrations that, in large part, do not reflect those found in human plasma. These media also lack additional plasma components needed to mimic the metabolic profile of human plasma. When studying cancer and other diseases, results with more physiological relevance will enable researchers to help improve their understanding of human function and illness.</p> </div> </div> </div> </div> <div class="cmp-p-sectioncontainer mt-l2 m--indent-l1"><div class="cmp-sectioncontainer" id="sectioncontainer-3325143475"> <div class="cmp-sectiontitle"> <h2 id="section-1" class="cmp-sectiontitle__text" data-anchor-nav-title="The HPLM solution">The HPLM solution</h2> </div> <div class="aem-Grid aem-Grid--12 aem-Grid--default--12 "> <div class="cmp-p-container p-l1 aem-GridColumn aem-GridColumn--default--12"> <div id="container-fbc942c5b4" class="cmp-container"> <div class="cmp-p-text mt-l1"> <div id="text-1549034375" class="cmp-text"> <p>Gibco HPLM contains the same salt concentrations found in human plasma, as well as the same concentrations of over 60 polar metabolites, such as amino acids, nucleic acids, sugars, and small organic acids. In resembling the natural cellular environment found in the body, HPLM helps provide researchers the ability to study the impact of physiologically relevant cell media on their specific applications.</p> <p> </p> <p>HPLM supplemented with fetal bovine serum (FBS) can support cell growth and viability comparable to those of conventional FBS-supplemented basal media formulations. For most cell lines, adaptation is not required to transition from conventional medium to HPLM.</p> <p> </p> <p>HPLM is beneficial to your cell culture experiments in several ways:</p> <ul> <li><b>Physiologically relevant</b>—formulated with more than 60 polar metabolites and salt concentrations that resemble the natural cellular environment found in the body</li> <li><b>Peer reviewed</b>—extensive research publications completed using HPLM formulation</li> <li><b>Easy to use</b>—direct replacement for your current media when supplemented with FBS</li> </ul> </div> </div> </div> </div> <div class="cmp-p-container p-l1 aem-GridColumn aem-GridColumn--default--12"> <div id="container-dd715cac02" class="cmp-container"> <div class="cmp-separator"> <hr class="cmp-separator__horizontal-rule"/> </div> </div> </div> </div> </div> </div> <div class="cmp-p-sectioncontainer mt-l2 m--indent-l1"><div class="cmp-sectioncontainer" id="sectioncontainer-e345ed5451"> <div class="cmp-sectiontitle"> <h2 id="section-2" class="cmp-sectiontitle__text" data-anchor-nav-title="Meet the inventor of HPLM">Meet the inventor of HPLM</h2> </div> <div class="aem-Grid aem-Grid--12 aem-Grid--default--12 "> <div class="cmp-p-container aem-GridColumn aem-GridColumn--default--12"> <div id="container-be8313751a" class="cmp-container"> <div class="aem-Grid aem-Grid--12 aem-Grid--default--12 aem-Grid--phone--12 "> <div class="cmp-p-container p-l1 aem-GridColumn--default--none aem-GridColumn--phone--none aem-GridColumn--phone--12 aem-GridColumn aem-GridColumn--offset--phone--0 aem-GridColumn--offset--default--0 aem-GridColumn--default--4"> <div id="container-ab932dfba7" class="cmp-container"> <div class="cmp-p-image"> <div data-cmp-is="image" data-cmp-src="/content/dam/LifeTech/global/life-sciences/CellCultureandTransfection/Images/2021/0221/Jason-R-Cantor.png" data-asset="/content/dam/LifeTech/global/life-sciences/CellCultureandTransfection/Images/2021/0221/Jason-R-Cantor.png" data-title="Jason R. Cantor " id="image-59264316" class="cmp-image " itemscope itemtype="http://schema.org/ImageObject"> <noscript data-cmp-hook-image="noscript"> <img src="/content/dam/LifeTech/global/life-sciences/CellCultureandTransfection/Images/2021/0221/Jason-R-Cantor.png" class="cmp-image__image" loading="lazy" itemprop="contentUrl" data-cmp-hook-image="image" alt="Jason R. Cantor " title="Jason R. Cantor "/> </noscript> <meta itemprop="caption" content="Jason R. Cantor "/> </div> <!-- Start Modal--> </div> <div class="cmp-p-ctaitem m--btn-outline m--center"><div class="cmp-ctaitem" id="ctaitem-c1c5b4561c"> <a class="cmp-ctaitem__anchor" href="https://players.brightcove.net/3663210762001/default_default/index.html?videoId=6239771407001" target="_blank"> <span class="cmp-ctaitem__text">Watch Jason&#39;s interview</span> </a> </div> </div> </div> </div> <div class="cmp-p-container p-l1 aem-GridColumn--default--none aem-GridColumn--phone--none aem-GridColumn--phone--12 aem-GridColumn aem-GridColumn--default--8 aem-GridColumn--offset--phone--0 aem-GridColumn--offset--default--0"> <div id="container-c5eb8877ce" class="cmp-container"> <div class="cmp-p-text mt-l1"> <div id="text-688899953" class="cmp-text"> <p>The inventor of human plasma-like medium is Jason R. Cantor.</p> <p> </p> <p>As a postdoc at the Whitehead Institute/MIT in Cambridge, Jason set out to create what would become human plasma-like medium (HPLM), a physiologic medium designed to more closely reflect the metabolic composition of human blood, thus permitting the study of cultured cells in biochemical conditions with greater relevance to human physiology.</p> <p> </p> <p>Cantor reported his development and initial studies using HPLM in early 2017 (Cell). Read his publication here: <a href="https://pubmed.ncbi.nlm.nih.gov/28388410">Physiologic Medium Rewires Cellular Metabolism and Reveals Uric Acid as an Endogenous Inhibitor of UMP Synthase</a>.</p> </div> </div> </div> </div> </div> </div> </div> <div class="cmp-p-container p-l1 aem-GridColumn aem-GridColumn--default--12"> <div id="container-f2aa2a34fe" class="cmp-container"> <div class="cmp-p-text mt-l1"> <div id="text-1578456068" class="cmp-text"> <p>We are proud to work with Jason to bring this innovation to market, and excited by the immense possibilities that HPLM could bring across diverse areas of the scientific community. As Jason notes, &quot;The recent development of physiologic media, like other efforts designed to address the modeling capacity of cell culture, holds immense potential to improve understanding and interpretation of diverse biological and pharmacological studies.&quot; Read more from his 2019 commentary here: <a href="https://pubmed.ncbi.nlm.nih.gov/31623927/">The Rise of Physiologic Media</a> .</p> <p> </p> <p>Jason is listed as an inventor on a patent application for HPLM assigned to Whitehead Institute.</p> </div> </div> </div> </div> <div class="cmp-p-container p-l1 mt-l1 aem-GridColumn aem-GridColumn--default--12"> <div id="container-2e7bf8b09b" class="cmp-container"> <div class="cmp-separator"> <hr class="cmp-separator__horizontal-rule"/> </div> </div> </div> </div> </div> </div> <div class="cmp-p-sectioncontainer mb-l4 p-l1"><div class="cmp-sectioncontainer" id="sectioncontainer-859b681df6"> <div class="cmp-sectiontitle"> <h2 id="research-results" class="cmp-sectiontitle__text" data-anchor-nav-title="Research results using HPLM">Research results using HPLM</h2> </div> <div class="aem-Grid aem-Grid--12 aem-Grid--default--12 "> <div class="cmp-p-container m--learning-center-container-border aem-GridColumn aem-GridColumn--default--12"> <div id="container-14c5665be2" class="cmp-container"> <div class="cmp-p-tabs m--step"><div id="tabs-c8bdf476d9" class="cmp-tabs" data-cmp-is="tabs"> <ol role="tablist" class="cmp-tabs__tablist" aria-multiselectable="false"> <li role="tab" id="tabs-c8bdf476d9-item-839c6a976f-tab" class="cmp-tabs__tab cmp-tabs__tab--active" aria-controls="tabs-c8bdf476d9-item-839c6a976f-tabpanel" tabindex="0" data-cmp-hook-tabs="tab">Performance</li> <li role="tab" id="tabs-c8bdf476d9-item-669b0da98d-tab" class="cmp-tabs__tab" aria-controls="tabs-c8bdf476d9-item-669b0da98d-tabpanel" tabindex="-1" data-cmp-hook-tabs="tab">Functionality</li> <li role="tab" id="tabs-c8bdf476d9-item-8d563ee7f0-tab" class="cmp-tabs__tab" aria-controls="tabs-c8bdf476d9-item-8d563ee7f0-tabpanel" tabindex="-1" data-cmp-hook-tabs="tab">Customer stories</li> <li role="tab" id="tabs-c8bdf476d9-item-2640c32c8a-tab" class="cmp-tabs__tab" aria-controls="tabs-c8bdf476d9-item-2640c32c8a-tabpanel" tabindex="-1" data-cmp-hook-tabs="tab">Webinar</li> <li role="tab" id="tabs-c8bdf476d9-item-b579f4e1e1-tab" class="cmp-tabs__tab" aria-controls="tabs-c8bdf476d9-item-b579f4e1e1-tabpanel" tabindex="-1" data-cmp-hook-tabs="tab">White paper</li> </ol> <div id="tabs-c8bdf476d9-item-839c6a976f" role="tabpanel" aria-labelledby="tabs-c8bdf476d9-item-839c6a976f" tabindex="0" class="cmp-tabs__tabpanel cmp-tabs__tabpanel--active" data-cmp-hook-tabs="tabpanel"><div class="cmp-p-container"> <div id="container-839c6a976f" class="cmp-container"> <div class="aem-Grid aem-Grid--12 aem-Grid--default--12 "> <div class="cmp-p-container p-l1 aem-GridColumn aem-GridColumn--default--12"> <div id="container-feac0e704a" class="cmp-container"> <div class="cmp-p-text mt-l1"> <div id="text-150259550" class="cmp-text"> <p>Research has shown that cellular performance is impacted by the use of HPLM, indicating that physiologic media can help increase the relevance of results from physiological studies.</p> <p> </p> </div> </div> <div class="cmp-p-title"><div id="title-ae960cfb66" class="cmp-title"> <h3 class="cmp-title__text">HPLM rewires cellular metabolism</h3> </div> </div> </div> </div> <div class="cmp-p-container aem-GridColumn--default--none aem-GridColumn aem-GridColumn--default--10 aem-GridColumn--offset--default--1"> <div id="container-7b64ed4c8c" class="cmp-container"> <div class="aem-Grid aem-Grid--default--10 aem-Grid--phone--10 aem-Grid--offset--phone--1 "> <div class="cmp-p-container p-l1 aem-GridColumn--default--none aem-GridColumn--phone--none aem-GridColumn--phone--10 aem-GridColumn aem-GridColumn--default--5 aem-GridColumn--offset--phone--0 aem-GridColumn--offset--default--0"> <div id="container-ed72fb4a22" class="cmp-container"> <div class="cmp-p-image"> <div data-cmp-is="image" data-cmp-src="/content/dam/LifeTech/global/life-sciences/CellCultureandTransfection/Images/2021/0221/graphical-abstract-hplm-rewires-cellular-metabolism-895x896.jpg" data-asset="/content/dam/LifeTech/global/life-sciences/CellCultureandTransfection/Images/2021/0221/graphical-abstract-hplm-rewires-cellular-metabolism-895x896.jpg" data-title="Physiologic medium rewires cellular metabolism and reveals uric acid as an endogenous inhibitor of UMP synthase" id="image-1891157022" class="cmp-image hand-icon" itemscope itemtype="http://schema.org/ImageObject"> <div data-toggle="modal" data-target="#modal-image-1891157022" class="modal-toggle"> <img src="/content/dam/LifeTech/global/life-sciences/CellCultureandTransfection/Images/2021/0221/graphical-abstract-hplm-rewires-cellular-metabolism-895x896.jpg" class="cmp-image__image" loading="lazy" itemprop="contentUrl" data-cmp-hook-image="image" alt="Diagram of the effects of different uric acid concentrations on uridine monophosphate synthase in humans and in mice" title="Physiologic medium rewires cellular metabolism and reveals uric acid as an endogenous inhibitor of UMP synthase"/> </div> <meta itemprop="caption" content="Physiologic medium rewires cellular metabolism and reveals uric acid as an endogenous inhibitor of UMP synthase"/> </div> <!-- Start Modal--> <div class="cmp-image-modal modal" id="modal-image-1891157022" tabindex="-1" role="dialog" aria-labelledby="modal-label-for-image-1891157022"> <div class="cmp-image-modal__body modal-body"> <div class="cmp-image-modal__header modal-header no-border"> <button type="button" class="cmp-image-modal__close close" data-dismiss="modal" aria-label="Close"> <span class="cmp-image-modal__close__icon" aria-hidden="true">&times;</span> </button> </div> <!-- set var for use expanded or main img--> <img loading="lazy" src="/content/dam/LifeTech/global/life-sciences/CellCultureandTransfection/Images/2021/0221/graphical-abstract-hplm-rewires-cellular-metabolism-895x896.jpg" class="cmp-image-modal__body__image" itemprop="contentUrl" data-cmp-hook-image="image" alt="Diagram of the effects of different uric acid concentrations on uridine monophosphate synthase in humans and in mice" title="Physiologic medium rewires cellular metabolism and reveals uric acid as an endogenous inhibitor of UMP synthase"/> </div> </div> </div> </div> </div> <div class="cmp-p-container aem-GridColumn--default--none aem-GridColumn--phone--none aem-GridColumn--phone--10 aem-GridColumn aem-GridColumn--default--5 aem-GridColumn--offset--phone--0 aem-GridColumn--offset--default--0"> <div id="container-e4d33d4c06" class="cmp-container"> <div class="cmp-p-text mt-l1"> <div id="text-1984782795" class="cmp-text"> <p><span class="font-size-14"><strong>Graphical abstract summary: </strong>“Among the most prominent was an inhibition of <em>de novo</em> pyrimidine synthesis—an effect traced to uric acid, which is 10-fold higher in the blood of humans than of mice and other non-primates. We find that uric acid directly inhibits uridine monophosphate synthase (UMPS) and consequently reduces the sensitivity of cancer cells to the chemotherapeutic agent 5-fluorouracil. Thus, media that better recapitulates the composition of human plasma reveals unforeseen metabolic wiring and regulation, suggesting that HPLM should be of broad utility.”</span></p> <p><span class="font-size-14"> </span></p> <p><span class="font-size-14">Reproduced with permission from: Cantor JR, Abu-Remaileh M, Kanarkek N et al. (2017) Physiologic medium rewires cellular metabolism and reveals uric acid as an endogenous inhibitor of UMP synthase. <em>Cell</em> 169: 258–272.E17. <a href="https://doi.org/10.1016/j.cell.2017.03.023">doi: 10.1016/j.cell.2017.03.023</a></span></p> </div> </div> </div> </div> </div> </div> </div> <div class="cmp-p-container p-l1 aem-GridColumn aem-GridColumn--default--12"> <div id="container-34e2d72ac0" class="cmp-container"> <div class="cmp-p-title"><div id="title-906550467c" class="cmp-title"> <h3 class="cmp-title__text">HPLM improves T lymphocyte activation</h3> </div> </div> </div> </div> <div class="cmp-p-container aem-GridColumn--default--none aem-GridColumn aem-GridColumn--default--10 aem-GridColumn--offset--default--1"> <div id="container-3dd83af13c" class="cmp-container"> <div class="aem-Grid aem-Grid--default--10 aem-Grid--phone--10 aem-Grid--offset--phone--1 "> <div class="cmp-p-container p-l1 aem-GridColumn--default--none aem-GridColumn--phone--none aem-GridColumn--phone--10 aem-GridColumn aem-GridColumn--default--5 aem-GridColumn--offset--phone--0 aem-GridColumn--offset--default--0"> <div id="container-ec222f1595" class="cmp-container"> <div class="cmp-p-image"> <div data-cmp-is="image" data-cmp-src="/content/dam/LifeTech/global/life-sciences/CellCultureandTransfection/Images/2021/0221/human-plasma-improves-lymphocyte-activation.jpg" data-asset="/content/dam/LifeTech/global/life-sciences/CellCultureandTransfection/Images/2021/0221/human-plasma-improves-lymphocyte-activation.jpg" data-title="Human plasma-like medium improves T lymphocyte activation" id="image-2076319252" class="cmp-image hand-icon" itemscope itemtype="http://schema.org/ImageObject"> <div data-toggle="modal" data-target="#modal-image-2076319252" class="modal-toggle"> <img src="/content/dam/LifeTech/global/life-sciences/CellCultureandTransfection/Images/2021/0221/human-plasma-improves-lymphocyte-activation.jpg" class="cmp-image__image" loading="lazy" itemprop="contentUrl" data-cmp-hook-image="image" alt="Diagram of the effects of different uric acid concentrations on uridine monophosphate synthase in humans and in mice" title="Human plasma-like medium improves T lymphocyte activation"/> </div> <meta itemprop="caption" content="Human plasma-like medium improves T lymphocyte activation"/> </div> <!-- Start Modal--> <div class="cmp-image-modal modal" id="modal-image-2076319252" tabindex="-1" role="dialog" aria-labelledby="modal-label-for-image-2076319252"> <div class="cmp-image-modal__body modal-body"> <div class="cmp-image-modal__header modal-header no-border"> <button type="button" class="cmp-image-modal__close close" data-dismiss="modal" aria-label="Close"> <span class="cmp-image-modal__close__icon" aria-hidden="true">&times;</span> </button> </div> <!-- set var for use expanded or main img--> <img loading="lazy" src="/content/dam/LifeTech/global/life-sciences/CellCultureandTransfection/Images/2021/0221/human-plasma-improves-lymphocyte-activation.jpg" class="cmp-image-modal__body__image" itemprop="contentUrl" data-cmp-hook-image="image" alt="Diagram of the effects of different uric acid concentrations on uridine monophosphate synthase in humans and in mice" title="Human plasma-like medium improves T lymphocyte activation"/> </div> </div> </div> </div> </div> <div class="cmp-p-container aem-GridColumn--default--none aem-GridColumn--phone--none aem-GridColumn--phone--10 aem-GridColumn aem-GridColumn--default--5 aem-GridColumn--offset--phone--0 aem-GridColumn--offset--default--0"> <div id="container-1164bed7f8" class="cmp-container"> <div class="cmp-p-text mt-l1"> <div id="text-1933529731" class="cmp-text"> <p><span class="font-size-14"><strong>Graphical abstract summary: </strong>“Among the most prominent was an inhibition of <em>de novo</em> pyrimidine synthesis—an effect traced to uric acid, which is 10-fold higher in the blood of humans than of mice and other non-primates. We find that uric acid directly inhibits uridine monophosphate synthase (UMPS) and consequently reduces the sensitivity of cancer cells to the chemotherapeutic agent 5-fluorouracil. Thus, media that better recapitulates the composition of human plasma reveals unforeseen metabolic wiring and regulation, suggesting that HPLM should be of broad utility.”</span></p> <p><span class="font-size-14"> </span></p> <p><span class="font-size-14">Reproduced with permission from: Cantor JR, Abu-Remaileh M, Kanarkek N et al. (2017) Physiologic medium rewires cellular metabolism and reveals uric acid as an endogenous inhibitor of UMP synthase. <em>Cell</em> 169: 258–272.E17. <a href="https://doi.org/10.1016/j.cell.2017.03.023">doi: 10.1016/j.cell.2017.03.023</a></span></p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div id="tabs-c8bdf476d9-item-669b0da98d" role="tabpanel" aria-labelledby="tabs-c8bdf476d9-item-669b0da98d" tabindex="0" class="cmp-tabs__tabpanel" data-cmp-hook-tabs="tabpanel"><div class="cmp-p-container"> <div id="container-669b0da98d" class="cmp-container"> <div class="aem-Grid aem-Grid--12 aem-Grid--default--12 "> <div class="cmp-p-container p-l1 aem-GridColumn aem-GridColumn--default--12"> <div id="container-16d598da52" class="cmp-container"> <div class="cmp-p-text mt-l1"> <div id="text-360274627" class="cmp-text"> <p>The functional characteristics of cells, including morphology and growth, in HPLM are comparable to those in conventional basal media formulations.</p> <p> </p> </div> </div> <div class="cmp-p-title"><div id="title-a417c429e7" class="cmp-title"> <h3 class="cmp-title__text">Human plasma-like medium maintains cell morphology</h3> </div> </div> </div> </div> <div class="cmp-p-container p-l1 aem-GridColumn--default--none aem-GridColumn aem-GridColumn--default--10 aem-GridColumn--offset--default--1"> <div id="container-1b90af23c6" class="cmp-container"> <div class="cmp-p-image"> <div data-cmp-is="image" data-cmp-src="/content/dam/LifeTech/global/life-sciences/CellCultureandTransfection/Images/2021/0221/gibco-hplm-supports-mcf7-cell-culture.jpg" data-asset="/content/dam/LifeTech/global/life-sciences/CellCultureandTransfection/Images/2021/0221/gibco-hplm-supports-mcf7-cell-culture.jpg" data-title="Gibco HPLM supports MCF7 cell morphology" id="image-2041059570" class="cmp-image " itemscope itemtype="http://schema.org/ImageObject"> <noscript data-cmp-hook-image="noscript"> <img src="/content/dam/LifeTech/global/life-sciences/CellCultureandTransfection/Images/2021/0221/gibco-hplm-supports-mcf7-cell-culture.jpg" class="cmp-image__image" loading="lazy" itemprop="contentUrl" data-cmp-hook-image="image" alt="2-panel brightfield microscopic views showing that MCF7 cells growing in either DMEM or HPLM exhibit the same morphologies" title="Gibco HPLM supports MCF7 cell morphology"/> </noscript> <meta itemprop="caption" content="Gibco HPLM supports MCF7 cell morphology"/> </div> <!-- Start Modal--> </div> <div class="cmp-p-text mt-l1"> <div id="text-488669432" class="cmp-text"> <p><span class="font-size-14"><strong>Figure 1. Gibco HPLM supports MCF7 cell culture. </strong>MCF7 breast adenocarcinoma cells were cultured in DMEM <a href="/order/catalog/product/10566016">(Cat. No. 10566016)</a> or Human Plasma-Like Medium (HPLM, <a href="/order/catalog/product/A4899101">Cat. No. A4899101)</a> supplemented with 10% FBS <a href="/order/catalog/product/A3840101">(Cat. No. A3840101)</a>.</span></p> </div> </div> </div> </div> <div class="cmp-p-container p-l1 aem-GridColumn--default--none aem-GridColumn aem-GridColumn--default--10 aem-GridColumn--offset--default--1"> <div id="container-e939393596" class="cmp-container"> <div class="cmp-p-image"> <div data-cmp-is="image" data-cmp-src="/content/dam/LifeTech/global/life-sciences/CellCultureandTransfection/Images/2021/0221/gibco-hplm-supports-HeLa-cell-culture.jpg" data-asset="/content/dam/LifeTech/global/life-sciences/CellCultureandTransfection/Images/2021/0221/gibco-hplm-supports-HeLa-cell-culture.jpg" data-title="Gibco HPLM supports MCF7 cell morphology" id="image-1744625569" class="cmp-image " itemscope itemtype="http://schema.org/ImageObject"> <noscript data-cmp-hook-image="noscript"> <img src="/content/dam/LifeTech/global/life-sciences/CellCultureandTransfection/Images/2021/0221/gibco-hplm-supports-HeLa-cell-culture.jpg" class="cmp-image__image" loading="lazy" itemprop="contentUrl" data-cmp-hook-image="image" alt="2-panel brightfield microscopic views showing that MCF7 cells growing in either DMEM or HPLM exhibit the same morphologies" title="Gibco HPLM supports MCF7 cell morphology"/> </noscript> <meta itemprop="caption" content="Gibco HPLM supports MCF7 cell morphology"/> </div> <!-- Start Modal--> </div> <div class="cmp-p-text mt-l1"> <div id="text-2021611003" class="cmp-text"> <p><span class="font-size-14"><strong>Figure 2. Gibco HPLM supports HeLa cell culture.</strong> HeLa human cervical adenocarcinoma cells were cultured in DMEM <a href="/order/catalog/product/11965092">(Cat. No. 11965092)</a> or Human Plasma-Like Medium (HPLM, <a href="/order/catalog/product/A4899101">Cat. No. A4899101)</a> supplemented with 10% FBS <a href="/order/catalog/product/A3840101">(Cat. No. A3840101)</a>.</span></p> </div> </div> </div> </div> <div class="cmp-p-container p-l1 aem-GridColumn--default--none aem-GridColumn aem-GridColumn--default--10 aem-GridColumn--offset--default--1"> <div id="container-4bf0caebfd" class="cmp-container"> <div class="cmp-p-image"> <div data-cmp-is="image" data-cmp-src="/content/dam/LifeTech/global/life-sciences/CellCultureandTransfection/Images/2021/0221/gibco-hplm-supports-LNCaP-cell-culture.jpg" data-asset="/content/dam/LifeTech/global/life-sciences/CellCultureandTransfection/Images/2021/0221/gibco-hplm-supports-LNCaP-cell-culture.jpg" data-title="Gibco HPLM supports LNCaP cell morphology" id="image-649580448" class="cmp-image " itemscope itemtype="http://schema.org/ImageObject"> <noscript data-cmp-hook-image="noscript"> <img src="/content/dam/LifeTech/global/life-sciences/CellCultureandTransfection/Images/2021/0221/gibco-hplm-supports-LNCaP-cell-culture.jpg" class="cmp-image__image" loading="lazy" itemprop="contentUrl" data-cmp-hook-image="image" alt="2-panel brightfield microscopic views showing that LNCaP cells growing in either DMEM or HPLM exhibit the same morphologies" title="Gibco HPLM supports LNCaP cell morphology"/> </noscript> <meta itemprop="caption" content="Gibco HPLM supports LNCaP cell morphology"/> </div> <!-- Start Modal--> </div> <div class="cmp-p-text mt-l1"> <div id="text-851917466" class="cmp-text"> <p><span class="font-size-14"><strong>Figure 3. Gibco HPLM supports LNCaP cell culture.</strong> LNCaP human metastatic prostate carcinoma cells were cultured in RPMI 1640 (left; <a href="/order/catalog/product/61870036">Cat. No. 61870036</a>) or HPLM (right; <a href="/order/catalog/product/A4899101">Cat. No. A4899101)</a> supplemented with 10% FBS <a href="/order/catalog/product/A3840101">(Cat. No. A3840101)</a>.</span></p> </div> </div> </div> </div> <div class="cmp-p-container p-l1 aem-GridColumn aem-GridColumn--default--12"> <div id="container-45021c83fe" class="cmp-container"> <div class="cmp-p-title"><div id="title-8520c4daec" class="cmp-title"> <h3 class="cmp-title__text">Human plasma-like medium maintains cell growth</h3> </div> </div> </div> </div> <div class="cmp-p-container p-l1 aem-GridColumn--default--none aem-GridColumn aem-GridColumn--default--10 aem-GridColumn--offset--default--1"> <div id="container-728ac487b7" class="cmp-container"> <div class="cmp-p-image"> <div data-cmp-is="image" data-cmp-src="/content/dam/LifeTech/global/life-sciences/CellCultureandTransfection/Images/2021/0221/gibco-hplm-supports-comparable-growth-rates-continuous-culture.jpg" data-asset="/content/dam/LifeTech/global/life-sciences/CellCultureandTransfection/Images/2021/0221/gibco-hplm-supports-comparable-growth-rates-continuous-culture.jpg" data-title="Gibco HPLM supports comparable growth rates in continuous culture" id="image-1320166855" class="cmp-image " itemscope itemtype="http://schema.org/ImageObject"> <noscript data-cmp-hook-image="noscript"> <img src="/content/dam/LifeTech/global/life-sciences/CellCultureandTransfection/Images/2021/0221/gibco-hplm-supports-comparable-growth-rates-continuous-culture.jpg" class="cmp-image__image" loading="lazy" itemprop="contentUrl" data-cmp-hook-image="image" alt="4-panel bar charts showing comparable doubling times for 4 cell lines in DMEM and in HPLM" title="Gibco HPLM supports comparable growth rates in continuous culture"/> </noscript> <meta itemprop="caption" content="Gibco HPLM supports comparable growth rates in continuous culture"/> </div> <!-- Start Modal--> </div> <div class="cmp-p-text mt-l1"> <div id="text-1897397357" class="cmp-text"> <p><span class="font-size-14"><strong>Figure 4. Gibco HPLM supports comparable growth rates in continuous culture. </strong>Tumor cell lines MCF7, HeLa, A549, and THP-1 were grown in DMEM (blue) or HPLM (red) supplemented with 10% FBS <a href="/order/catalog/product/A3840101">(Cat. No. A3840101)</a> for five passages. Cell number was assessed at the end of each passage and used to calculate the average population doubling time for each culture.</span></p> </div> </div> </div> </div> <div class="cmp-p-container p-l1 aem-GridColumn aem-GridColumn--default--12"> <div id="container-9843da81f3" class="cmp-container"> <div class="cmp-p-title"><div id="title-bd28bdd7ad" class="cmp-title"> <h3 class="cmp-title__text">Human plasma-like medium supports cell growth in multiple cell types</h3> </div> </div> </div> </div> <div class="cmp-p-container p-l1 aem-GridColumn aem-GridColumn--default--12"> <div id="container-2c1dfd3111" class="cmp-container"> <div class="cmp-p-text m--header"> <div id="text-1097256135" class="cmp-text"> <h5>Table 1. Cell types successfully grown in human plasma-like medium</h5> <table cellpadding="1" cellspacing="0" border="1" width="100%"> <tbody><tr><td width="50%"><h5>Cell type tested</h5> </td> <td width="50%"><h5>Cell origin</h5> </td> </tr><tr><td>A375, adherent</td> <td>Malignant melanoma</td> </tr><tr><td>A549, adherent</td> <td>Lung carcinoma</td> </tr><tr><td>HCT116, adherent</td> <td>Colorectal carcinoma</td> </tr><tr><td>HeLa, adherent</td> <td>Cervical adenocarcinoma</td> </tr><tr><td>Jurkat, suspension</td> <td>T cell leukemia</td> </tr><tr><td>LNCaP, adherent</td> <td>Metastatic prostate carcinoma</td> </tr><tr><td>MCF-7, adherent</td> <td>Metastatic breast cancer</td> </tr><tr><td>MDA-MB-231, adherent</td> <td>Metastatic breast cancer</td> </tr><tr><td>NK, primary, suspension</td> <td>Lymphocyte, blood</td> </tr><tr><td>NOMO-1, suspension</td> <td>Monoblastic/monocytic leukemia</td> </tr><tr><td>PLB-985, suspension</td> <td>Myeloid leukemia</td> </tr><tr><td>Sp2, suspension</td> <td>Mouse B lymphocyte</td> </tr><tr><td>THP-1, suspension</td> <td>Monocytic leukemia</td> </tr><tr><td>U-2 OS, adherent</td> <td>Osteosarcoma</td> </tr><tr><td>WM115, adherent</td> <td>Malignant melanoma</td> </tr></tbody></table> </div> </div> </div> </div> </div> </div> </div> </div> <div id="tabs-c8bdf476d9-item-8d563ee7f0" role="tabpanel" aria-labelledby="tabs-c8bdf476d9-item-8d563ee7f0" tabindex="0" class="cmp-tabs__tabpanel" data-cmp-hook-tabs="tabpanel"><div class="cmp-p-container"> <div id="container-8d563ee7f0" class="cmp-container"> <div class="cmp-p-container p-l1"> <div id="container-98ca8c746c" class="cmp-container"> <div class="cmp-p-title"><div id="title-ac6b6dc65d" class="cmp-title"> <h3 class="cmp-title__text">The following customer stories feature the work of our Gibco HPLM product testers</h3> </div> </div> </div> </div> <div class="cmp-p-container"> <div id="container-bb349897e2" class="cmp-container"> </div> </div> <div class="cmp-p-container p-l1"> <div id="container-20d6fabe7c" class="cmp-container"> <div class="cmp-p-testimonial m--no-border"> <div class="cmp-testimonial cta-container" data-cmp-hook-cta="ctapanel"> <div class="cmp-testimonial__message"> <p>“We used the HPLM media with cancer cell lines from different tissues and different mutation background. Our overall impression of HPLM is quite positive. HPLM media was suitable for all the tested cancer cell lines. Cells were easily and quickly adapted to the HPLM without affecting viability and cell culture performance. However, we detected relevant impact of cell proliferation, metabolism and mitochondrial function in cells grown in HPLM as compared with classical media. After our experience using HPLM in cancer cell models we consider it as the best choice to get more physiological data.”</p> </div> <div class="cmp-testimonial__author"> <div class="cmp-testimonial__author-image-wrapper"> <img class="cmp-testimonial__author-image" src="/content/dam/LifeTech/global/life-sciences/CellCultureandTransfection/Images/2021/0221/Omar-Torres-headshot.png"/> </div> <div class="cmp-testimonial__author-info"> <h3 class="cmp-testimonial__author-name">Omar Torres-Quesada </h3> <p class="cmp-testimonial__author-credentials">PhD, Postdoctoral Researcher at University of Innsbruck </p> <p class="cmp-testimonial__author-line2">Austria</p> <p class="cmp-testimonial__author-line3"></p> </div> </div> </div> </div> <div class="cmp-separator"> <hr class="cmp-separator__horizontal-rule"/> </div> </div> </div> <div class="cmp-p-container p-l1"> <div id="container-a37a8f1128" class="cmp-container"> <div class="cmp-p-testimonial m--no-border"> <div class="cmp-testimonial cta-container" data-cmp-hook-cta="ctapanel"> <div class="cmp-testimonial__message"> <p>“Immunometabolism is an exciting area of scientific investigation that has immense potential for the development of new therapeutics. It is becoming clear that how immune cells rewire their metabolism after activation depends on what nutrients are available and in what quantities. Since we study metabolite transport in primary human immune cells, we find HPLM media to be essential for modeling metabolic flux in the most physiologically relevant way possible. We have extensively vetted the use of HPLM across CD4 T helper cell lineages and find that it supports both proliferation and effector function.&quot;</p> </div> <div class="cmp-testimonial__author"> <div class="cmp-testimonial__author-image-wrapper"> <img class="cmp-testimonial__author-image" src="/content/dam/LifeTech/global/life-sciences/CellCultureandTransfection/Images/2021/0221/Justin-Rettenmaier-headshot.png"/> </div> <div class="cmp-testimonial__author-info"> <h3 class="cmp-testimonial__author-name">Justin Rettenmaier, </h3> <p class="cmp-testimonial__author-credentials">Associate Director at Jnana Therapeutics </p> <p class="cmp-testimonial__author-line2">Boston, MA</p> <p class="cmp-testimonial__author-line3"></p> </div> </div> </div> </div> <div class="cmp-separator"> <hr class="cmp-separator__horizontal-rule"/> </div> </div> </div> <div class="cmp-p-container p-l1"> <div id="container-254c99e11a" class="cmp-container"> <div class="cmp-p-testimonial m--no-border"> <div class="cmp-testimonial cta-container" data-cmp-hook-cta="ctapanel"> <div class="cmp-testimonial__message"> <p>&quot;Standard cell culture media, including the Dulbecco’s Modified Eagle Medium (DMEM), contain a non-physiological excess of nutrients, including glucose and glutamine. At the same time, they are low on uric acid. Nutrient availability, however, is a most critical factor for the regulation of mTOR calling for a careful consideration of culture conditions. Therefore, we employed Human Plasma Like Medium (HPLM) to gain a better understanding of mTORC1 regulation under physiological nutrient abundance. In line with mTOR’s intricate connection to nutrient sensing pathways, mTORC1 activity, as measured by Thr389 phosphorylation of S6K, was lower when U2OS cells were cultured in HPLM instead of DMEM. In HPLM media and irrespective of any treatment, AKT and the glucose-sensing AMPK were activated. Most importantly, however, we found that p53 was required to sustain low mTORC1 activity under HPLM culture conditions irrespective of Nutlin-3a treatment. Together, our investigation using HPLM revealed a nutrient-dependent role of p53 in mTORC1 inhibition.&quot;</p> </div> <div class="cmp-testimonial__author"> <div class="cmp-testimonial__author-image-wrapper"> <img class="cmp-testimonial__author-image" src="/content/dam/LifeTech/global/life-sciences/CellCultureandTransfection/Images/2021/0221/Martin-Fischer-headshot.png"/> </div> <div class="cmp-testimonial__author-info"> <h3 class="cmp-testimonial__author-name">Martin Fischer </h3> <p class="cmp-testimonial__author-credentials"> Principal Investigator at Leibniz Institute on Aging </p> <p class="cmp-testimonial__author-line2">Germany</p> <p class="cmp-testimonial__author-line3"></p> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div id="tabs-c8bdf476d9-item-2640c32c8a" role="tabpanel" aria-labelledby="tabs-c8bdf476d9-item-2640c32c8a" tabindex="0" class="cmp-tabs__tabpanel" data-cmp-hook-tabs="tabpanel"><div class="cmp-p-container"> <div id="container-2640c32c8a" class="cmp-container"> <div class="cmp-p-container"> <div id="container-9a52066161" class="cmp-container"> <div class="aem-Grid aem-Grid--12 aem-Grid--default--12 aem-Grid--phone--12 "> <div class="cmp-p-container p-l1 aem-GridColumn--default--none aem-GridColumn--phone--none aem-GridColumn--phone--12 aem-GridColumn aem-GridColumn--offset--phone--0 aem-GridColumn--offset--default--0 aem-GridColumn--default--4"> <div id="container-5fe88e5574" class="cmp-container"> <div class="cmp-p-image"> <div data-cmp-is="image" data-cmp-src="/content/dam/LifeTech/global/life-sciences/CellCultureandTransfection/Images/2021/0221/Jason-R-Cantor.png" data-asset="/content/dam/LifeTech/global/life-sciences/CellCultureandTransfection/Images/2021/0221/Jason-R-Cantor.png" data-title="Jason R. Cantor " id="image-347360054" class="cmp-image " itemscope itemtype="http://schema.org/ImageObject"> <noscript data-cmp-hook-image="noscript"> <img src="/content/dam/LifeTech/global/life-sciences/CellCultureandTransfection/Images/2021/0221/Jason-R-Cantor.png" class="cmp-image__image" loading="lazy" itemprop="contentUrl" data-cmp-hook-image="image" alt="Jason R. Cantor " title="Jason R. Cantor "/> </noscript> <meta itemprop="caption" content="Jason R. Cantor "/> </div> <!-- Start Modal--> </div> </div> </div> <div class="cmp-p-container p-l1 aem-GridColumn--default--none aem-GridColumn--phone--none aem-GridColumn--phone--12 aem-GridColumn aem-GridColumn--default--8 aem-GridColumn--offset--phone--0 aem-GridColumn--offset--default--0"> <div id="container-ab3e3980cb" class="cmp-container"> <div class="cmp-p-text mt-l1"> <div id="text-1556669111" class="cmp-text"> <h4>Webinar: Physiologic medium to study human cell biology</h4> <h4> </h4> <p>Environmental factors influence human cell physiology and can also affect drug efficacy, but existing model systems used to study human cells have limitations for understanding these contributions. In this webinar, Dr. Jason Cantor will discuss the initial development and use of human plasma-like medium (HPLM), a physiologic medium designed to more closely reflect the metabolic composition of human blood. By examining human cancer cell lines in HPLM versus traditional media, Dr. Cantor and colleagues have recently shown that HPLM has widespread effects on metabolism and gene essentiality, and further, that HPLM can be used to reveal new insights into metabolic regulation and drug efficacy.</p> <p> </p> <p><b>Speaker:</b> Jason R. Cantor, Investigator, Morgridge Institute for Research, Assistant Professor of Biochemistry, University of Wisconsin-Madison</p> </div> </div> </div> </div> </div> </div> </div> <div class="cmp-p-container p-l1"> <div id="container-919323034f" class="cmp-container"> <div class="cmp-p-text mt-l1"> <div id="text-468149560" class="cmp-text"> <p><strong>Webinar highlights:</strong></p> <ul> <li>Complete media, the workhorses of cell culture studies, typically consist of a basal medium that poorly resembles conditions encountered in the human body and a largely undefined serum supplement</li> <li>Human Plasma-Like Medium (HPLM) is a relatively new physiologic basal medium designed to more closely reflect the metabolic composition of human blood</li> <li>The development of physiologic media, like other efforts designed to address the modeling capacity of cell culture, holds immense potential to improve understanding and interpretation of biological and pharmacological studies</li> </ul> </div> </div> <div class="cmp-p-ctaitem"><div class="cmp-ctaitem" id="ctaitem-5f3b9b7f0c"> <a class="cmp-ctaitem__anchor" href="https://players.brightcove.net/3663210762001/default_default/index.html?videoId=6255132822001" target="_blank"> <span class="cmp-ctaitem__icon icon-24-arrow-right-bold"></span> <span class="cmp-ctaitem__text">Watch webinar</span> </a> </div> </div> </div> </div> </div> </div> </div> <div id="tabs-c8bdf476d9-item-b579f4e1e1" role="tabpanel" aria-labelledby="tabs-c8bdf476d9-item-b579f4e1e1" tabindex="0" class="cmp-tabs__tabpanel" data-cmp-hook-tabs="tabpanel"><div class="cmp-p-container"> <div id="container-b579f4e1e1" class="cmp-container"> <div class="aem-Grid aem-Grid--12 aem-Grid--default--12 "> <div class="cmp-p-container p-l1 aem-GridColumn aem-GridColumn--default--12"> <div id="container-c22ab6f2e2" class="cmp-container"> <div class="cmp-p-text mt-l1"> <div id="text-904237284" class="cmp-text"> <h4>Assessment of cancer spheroid formation in Human Plasma-Like Medium</h4> <p> </p> <p>Human Plasma-Like Medium (HPLM) is a cell growth formulation designed to mimic the metabolic profile of human plasma to help maintain the physiological state of cells.</p> <p>We demonstrate the capability of HPLM to support the growth of cancer spheroids in several well-studied cancer cell lines</p> </div> </div> </div> </div> <div class="cmp-p-container p-l1 aem-GridColumn--default--none aem-GridColumn aem-GridColumn--default--10 aem-GridColumn--offset--default--1"> <div id="container-4783ebb893" class="cmp-container"> <div class="cmp-p-image"> <div data-cmp-is="image" data-cmp-src="/content/dam/LifeTech/global/life-sciences/bid/cell-biology/2022/08/HPLM Child - White Paper Tab - HPLM-supports-3D-spheroid-formation.png" data-asset="/content/dam/LifeTech/global/life-sciences/bid/cell-biology/2022/08/HPLM Child - White Paper Tab - HPLM-supports-3D-spheroid-formation.png" data-title="Cancer spheroids grown in different media types" id="image-1316666953" class="cmp-image " itemscope itemtype="http://schema.org/ImageObject"> <noscript data-cmp-hook-image="noscript"> <img src="/content/dam/LifeTech/global/life-sciences/bid/cell-biology/2022/08/HPLM%20Child%20-%20White%20Paper%20Tab%20-%20HPLM-supports-3D-spheroid-formation.png" class="cmp-image__image" loading="lazy" itemprop="contentUrl" data-cmp-hook-image="image" alt="Microscopy images of spheroids for different cell types grown in standard RPMI or HPLM medium" title="Cancer spheroids grown in different media types"/> </noscript> <meta itemprop="caption" content="Cancer spheroids grown in different media types"/> </div> <!-- Start Modal--> </div> <div class="cmp-p-text mt-l1"> <div id="text-319247057" class="cmp-text"> <p><span class="font-size-14"><strong>Figure 5. HPLM supports 3D spheroid formation.</strong> Representative images of spheroids from various cell types cultured in RPMI standard medium and Human Plasma-Like Medium (HPLM) that were grown for five days. Images were captured using the Invitrogen <a href="/sg/en/home/life-science/cell-analysis/cellular-imaging/evos-cell-imaging-systems/models/evos-m7000.html">EVOS M7000 Imaging System</a>. Scale bar = 650 µm.</span></p> </div> </div> </div> </div> <div class="cmp-p-container p-l1 aem-GridColumn aem-GridColumn--default--12"> <div id="container-42fc0577e6" class="cmp-container"> <div class="cmp-p-ctaitem"><div class="cmp-ctaitem" id="ctaitem-81abcc22e1"> <a class="cmp-ctaitem__anchor" href="https://assets.thermofisher.com/TFS-Assets/BID/Reference-Materials/assessment-cancer-spheroid-formation-human-plasma-white-paper.pdf" target="_blank"> <span class="cmp-ctaitem__icon icon-24-arrow-right-bold"></span> <span class="cmp-ctaitem__text">Access full white paper</span> </a> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="cmp-p-sectioncontainer p-l1"><div class="cmp-sectioncontainer" id="sectioncontainer-3b07cbf87e"> <div class="cmp-sectiontitle"> <h2 id="section-4" class="cmp-sectiontitle__text" data-anchor-nav-title="Recent publications using HPLM">Recent publications using HPLM</h2> </div> <div class="aem-Grid aem-Grid--12 aem-Grid--default--12 "> <div class="cmp-p-container m--learning-center-container-border mb-l3 aem-GridColumn aem-GridColumn--default--12"> <div id="container-d603a69819" class="cmp-container"> <div class="cmp-p-tabs m--step"><div id="tabs-1931d37397" class="cmp-tabs" data-cmp-is="tabs"> <ol role="tablist" class="cmp-tabs__tablist" aria-multiselectable="false"> <li role="tab" id="tabs-1931d37397-item-f3436ba140-tab" class="cmp-tabs__tab cmp-tabs__tab--active" aria-controls="tabs-1931d37397-item-f3436ba140-tabpanel" tabindex="0" data-cmp-hook-tabs="tab">Cancer</li> <li role="tab" id="tabs-1931d37397-item-75c3998a7b-tab" class="cmp-tabs__tab" aria-controls="tabs-1931d37397-item-75c3998a7b-tabpanel" tabindex="-1" data-cmp-hook-tabs="tab">Inmunology</li> <li role="tab" id="tabs-1931d37397-item-ce92916c7f-tab" class="cmp-tabs__tab" aria-controls="tabs-1931d37397-item-ce92916c7f-tabpanel" tabindex="-1" data-cmp-hook-tabs="tab">Metabolism</li> <li role="tab" id="tabs-1931d37397-item-a04d144305-tab" class="cmp-tabs__tab" aria-controls="tabs-1931d37397-item-a04d144305-tabpanel" tabindex="-1" data-cmp-hook-tabs="tab">Other research</li> </ol> <div id="tabs-1931d37397-item-f3436ba140" role="tabpanel" aria-labelledby="tabs-1931d37397-item-f3436ba140" tabindex="0" class="cmp-tabs__tabpanel cmp-tabs__tabpanel--active" data-cmp-hook-tabs="tabpanel"><div class="cmp-p-container p-l1"> <div id="container-f3436ba140" class="cmp-container"> <div class="aem-Grid aem-Grid--12 aem-Grid--default--12 "> <div class="cmp-p-text m--header aem-GridColumn aem-GridColumn--default--12"> <div id="text-1675264951" class="cmp-text"> <table cellpadding="1" cellspacing="0" border="1"> <tbody><tr><th><strong>Title</strong></th> <th><strong>Cell type(s)</strong></th> <th><strong>Research area(s)</strong></th> <th><strong>Assay type</strong></th> </tr><tr><td><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172426/">CRISPR screens in physiologic medium reveal conditionally essential genes in human cells</a></td> <td>K562, MOLM-13, SUDHL4, and NOMO1</td> <td>Cancer biology</td> <td>CRISPR, RNA-seq, metabolite profiling, enzyme activity</td> </tr><tr><td><a href="https://pubmed.ncbi.nlm.nih.gov/35985343/">De novo pyrimidine synthesis is a targetable vulnerability in IDH mutant glioma</a></td> <td>BT054 oligodendroglioma cells</td> <td>Cancer biology</td> <td>transduction, drug screening, metabolite analysis, mass spec, isotope tracing, western blotting</td> </tr><tr><td><a href="https://pubmed.ncbi.nlm.nih.gov/36284040/">Early reduction of glucose consumption is a biomarker of kinase inhibitor efficacy which can be reversed with GLUT1 overexpression in lung cancer cells</a></td> <td>PC9, H1229, H3122</td> <td>Cancer biology</td> <td>growth kinetics, drug screening, xenograft, transduction</td> </tr><tr><td><a href="https://pubmed.ncbi.nlm.nih.gov/35857801/">Activating mTOR mutations are detrimental in nutrient-poor conditions</a></td> <td> primary mouse embryonic fibroblasts</td> <td>Cancer biology</td> <td>growth kinetics</td> </tr><tr><td><a href="https://pubmed.ncbi.nlm.nih.gov/38647418/">Therapeutic efficacy of RAS inhibitor trametinib using a juvenile myelomonocytic leukemia patient-derived xenograft model</a></td> <td> juvenile myelomonocytic leukemia (JMML) cells</td> <td>Immuno-oncology</td> <td>western blot</td> </tr></tbody></table> </div> </div> </div> </div> </div> </div> <div id="tabs-1931d37397-item-75c3998a7b" role="tabpanel" aria-labelledby="tabs-1931d37397-item-75c3998a7b" tabindex="0" class="cmp-tabs__tabpanel" data-cmp-hook-tabs="tabpanel"><div class="cmp-p-container p-l1"> <div id="container-75c3998a7b" class="cmp-container"> <div class="aem-Grid aem-Grid--12 aem-Grid--default--12 "> <div class="cmp-p-text m--header aem-GridColumn aem-GridColumn--default--12"> <div id="text-1703894102" class="cmp-text"> <table cellpadding="1" cellspacing="0" border="1"> <tbody><tr><th><strong>Title</strong></th> <th><strong>Cell type(s)</strong></th> <th><strong>Research area(s)</strong></th> <th><strong>Assay type</strong></th> </tr><tr><td><a href="https://pubmed.ncbi.nlm.nih.gov/31887663/">Human Plasma-like Medium improves T lymphocyte activation</a></td> <td>human and mouse T cells</td> <td>Immunology</td> <td>transcriptome analysis, NGS</td> </tr><tr><td><a href="https://pubmed.ncbi.nlm.nih.gov/34767747/">MTHFD2 is a metabolic checkpoint controlling effector and regulatory T cell fate and function</a></td> <td>primary human T cells</td> <td>Immunology</td> <td>T cell activation, metabolomics, mass spec, next-gen bisulfite sequencing, IHC, flow cytometry</td> </tr><tr><td><a href="https://pubmed.ncbi.nlm.nih.gov/34341788/">Single-cell profiling of the antigen-specific response to BNT162b2 SARS-CoV-2 RNA vaccine</a></td> <td>human PBMC</td> <td>Immunology</td> <td>LIBRA-seq, single-cell RNA-seq, flow cytometry</td> </tr><tr><td><a href="https://pubmed.ncbi.nlm.nih.gov/34717796/">Plasmacytoid dendritic cell activation is dependent on coordinated expression of distinct amino acid transporters</a></td> <td>plasmacytoid dendritic cells isolated from PBMCs</td> <td>Immunology</td> <td>ELISA, flow cytometry, isotope tracing, single-cell RNA-seq, CHIP-seq, IHC</td> </tr><tr><td><a href="https://pubmed.ncbi.nlm.nih.gov/36028574/">mTOR regulation of metabolism limits LPS-induced monocyte inflammatory and procoagulant responses</a></td> <td>human PBMC</td> <td>Immunology</td> <td>ELISA, flow cytometry, metabolite profiling, isotope labelling, RNA-seq, ChIP</td> </tr><tr><td><a href="https://pubmed.ncbi.nlm.nih.gov/36758834/">Obesity and inflammation influence pharmacokinetic profiles of<br /> PEG-based nanoparticles</a></td> <td>Sk-Hep1 human liver adenocarcinoma cells, Tp1 cells</td> <td> Immunology, Obesity</td> <td>fluorescence imaging, flow cytometry</td> </tr><tr><td><a href="https://pubmed.ncbi.nlm.nih.gov/36890150/">Suppression of CEBPδ recovers exhaustion in anti-metastatic immune cells</a></td> <td>mouse NK cells</td> <td>Immunology</td> <td>siRNA mediated knockdown, tumoricidal assay</td> </tr></tbody></table> </div> </div> </div> </div> </div> </div> <div id="tabs-1931d37397-item-ce92916c7f" role="tabpanel" aria-labelledby="tabs-1931d37397-item-ce92916c7f" tabindex="0" class="cmp-tabs__tabpanel" data-cmp-hook-tabs="tabpanel"><div class="cmp-p-container p-l1"> <div id="container-ce92916c7f" class="cmp-container"> <div class="cmp-p-text m--header"> <div id="text-1287567248" class="cmp-text"> <table cellpadding="1" cellspacing="0" border="1"> <tbody><tr><th><strong>Title</strong></th> <th><strong>Cell type(s)</strong></th> <th><strong>Research area(s)</strong></th> <th><strong>Assay type</strong></th> </tr><tr><td><a href="https://pubmed.ncbi.nlm.nih.gov/28388410/">Physiologic medium rewires cellular metabolism and reveals uric acid as an endogenous inhibitor of UMP synthase</a></td> <td>K562, KMS12BM, NOMO1, P12-Ichikawa, SEM, SUDHL4, 786-0, A549, MCF7, SW620, BJ, CLF-PED-015T, primary acute myeloid leukemia cells</td> <td>Cancer metabolism</td> <td>growth kinetics, metabolite quantification and analysis, cholesterol quantification, oxygen consumption</td> </tr><tr><td><a href="https://pubmed.ncbi.nlm.nih.gov/31961917/">Inhibiting both proline biosynthesis and lipogenesis synergistically suppresses tumor growth</a></td> <td>HeLa, MDA-MB-231, MCF-7, A549, HepG2, 8133, SKOV3, and mouse 4T1 cells</td> <td>Cancer metabolism</td> <td>electron production in metabolism, metabolite isotope tracing, RNA-seq</td> </tr><tr><td><a href="https://pubmed.ncbi.nlm.nih.gov/32268116/">ZBTB1 regulates asparagine synthesis and leukemia cell response to L-asparaginase</a></td> <td>CUTLL1, SUPT1, MOLM-13</td> <td>Cancer metabolism</td> <td>metabolite profiling, isotope tracing, ATAC-seq, mass spec</td> </tr><tr><td><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8845302/">Lineage-specific silencing of PSAT1 induces serine auxotrophy and sensitivity to dietary serine starvation in luminal breast tumors</a></td> <td> HCC1806, SUM149, BT549, HCC1937, HCC70, BT20, MCF7, MDA-MB-453, ZR75-1, EFM19, HCC1500, T47D</td> <td>Cancer metabolism</td> <td>metabolite analysis, cell proliferation, mass spec</td> </tr><tr><td><a href="https://pubmed.ncbi.nlm.nih.gov/33833463/">Mitochondrial NADP+ is essential for proline biosynthesis during cell growth</a></td> <td>HEK293E, HeLa, K562</td> <td>Cancer metabolism</td> <td>CRISPR, mitochondria isolation, spheroid growth, cell cycle, metabolic flux analysis, mass spec</td> </tr><tr><td><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285073/">Metabolic perturbations sensitize triple-negative breast cancers to apoptosis induced by BH3 mimetics</a></td> <td> HCC1143, HCC1937, MDA-MB-231, MDA-MB-468</td> <td>Cancer metabolism</td> <td>metabolite analysis, BH3 profiling, qPCR</td> </tr><tr><td><a href="https://pubmed.ncbi.nlm.nih.gov/34907345/">p53-mediated AKT and mTOR inhibition requires RFX7 and DDIT4 and depends on nutrient abundance</a></td> <td> U2OS, HCT116</td> <td>Cancer metabolism</td> <td> transfection, ChIP, western blotting</td> </tr><tr><td><a href="https://pubmed.ncbi.nlm.nih.gov/35130302/">Increased mitochondrial proline metabolism sustains proliferation and survival of colorectal cancer cells</a></td> <td>RKO</td> <td>Cancer metabolism</td> <td> transfection, cell proliferation, apoptosis, mass spec</td> </tr><tr><td><a href="https://pubmed.ncbi.nlm.nih.gov/36010911/">Human Plasma-Like Media fine tune mitochondrial function and alter drug sensitivity in cancer cell lines</a></td> <td>SW620, MCF7, A375</td> <td>Cancer metabolism</td> <td>cell proliferation, respirometry</td> </tr><tr><td><a href="https://pubmed.ncbi.nlm.nih.gov/36044390/">Human acute leukemia utilizes branched-chain amino acid catabolism to maintain stemness through regulating PRC2 function</a></td> <td>human primary AML and ALL cells</td> <td>Cancer metabolism</td> <td>metabolome analysis, flow cytometry, transplantation, RNA microarray, ChIP-seq, cell cycle, isotope tracing</td> </tr><tr><td><a href="https://pubmed.ncbi.nlm.nih.gov/36070681/">Methionine metabolism controls the B cell EBV epigenome and viral latency</a></td> <td>P3HR-1 Burkitt’s lymphoma cell</td> <td>Cancer metabolism</td> <td>CRISPR, MeDIP, ChIP, RNA-seq, mouse xenograft, metabolite profiling, IHC</td> </tr><tr><td><a href="https://pubmed.ncbi.nlm.nih.gov/36638190/">Elevated transferrin receptor impairs T cell metabolism and function in systemic lupus erythematosus</a></td> <td>mouse naïve T cells, patient-derived T cells</td> <td>Cancer metabolism</td> <td> CRISPR, RNA-seq, mass spec, IHC</td> </tr><tr><td><a href="https://pubmed.ncbi.nlm.nih.gov/37012496/">Formate overflow drives toxic folate trapping in MTHFD1 inhibited cancer cells</a></td> <td>SW620 (CLL-227), HCT116 (CLL-247), MDA-MB-468 (HTB-132) and MDA-MB-231 (HTB-26) cells</td> <td>Cancer metabolism</td> <td>drug affinity responsive target stability (DARTS) assay, cellular thermal shift assay (CETSA), stable isotope tracing, mass spec</td> </tr><tr><td><a href="https://www.cell.com/cell-metabolism/fulltext/S1550-4131(23)00178-X?_returnURL=https://linkinghub.elsevier.com/retrieve/pii/S155041312300178X?showall=true">Canagliflozin impairs T cell effector function via metabolic suppression in autoimmunity</a></td> <td>human PBMC-derived T cells</td> <td>T cell metabolism</td> <td>ELISA, flow cytometry, metabolic analysis by extracellular flux analyzer, western blot, stable isotope tracer analysis (SITA) by LC-MS, RNA-seq, proteomic analysis, mass spec</td> </tr><tr><td><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11102027/">Iron is critical for mucosal-associated invariant T cell metabolism and effector functions</a></td> <td>human PBMCs</td> <td>T cell metabolism</td> <td>transferrin uptake assay</td> </tr><tr><td><a href="https://pubmed.ncbi.nlm.nih.gov/38858374/">Targeting fatty acid synthase in preclinical models of TNBC brain metastases synergizes with SN-38 and impairs invasion</a></td> <td>MDA-MB-231</td> <td>Cancer metabolism</td> <td>drug screening, RNA expression</td> </tr><tr><td><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11294174/">Hypoxanthine in the microenvironment can enable thiopurine resistance in acute lymphoblastic leukemia</a></td> <td>NALM-6, REH, SEM, CEM, Jurkat</td> <td>Cancer metabolism</td> <td>drug assay (viability readouts using Cell-Titer Glo, Caspase 3/7 assay)</td> </tr><tr><td><a href="https://pubmed.ncbi.nlm.nih.gov/37333068/">Conditional lethality profiling reveals anticancer mechanisms of action and drug-nutrient interactions</a></td> <td>K562, SEM, NOMO1, P12-Ichikawa</td> <td>Cancer metabolism</td> <td>Drug screening</td> </tr></tbody></table> </div> </div> </div> </div> </div> <div id="tabs-1931d37397-item-a04d144305" role="tabpanel" aria-labelledby="tabs-1931d37397-item-a04d144305" tabindex="0" class="cmp-tabs__tabpanel" data-cmp-hook-tabs="tabpanel"><div class="cmp-p-container p-l1"> <div id="container-a04d144305" class="cmp-container"> <div class="cmp-p-text m--header"> <div id="text-110434550" class="cmp-text"> <table cellpadding="1" cellspacing="0" border="1"> <tbody><tr><th><strong>Title</strong></th> <th><strong>Cell type(s)</strong></th> <th><strong>Research area(s)</strong></th> <th><strong>Assay type</strong></th> </tr><tr><td><a href="https://pubmed.ncbi.nlm.nih.gov/34987071/">Nickels and tines: the myth of nickel allergy in intracranial stents</a></td> <td>not applicable</td> <td>Medicine/surgery</td> <td>nickel allergy test</td> </tr><tr><td><a href="https://pubmed.ncbi.nlm.nih.gov/36811942/">Generation of induced pluripotent stem cell-derived beta-cells in blood amino acids-like medium</a></td> <td>human iPSCs</td> <td> Stem cell differentiation</td> <td>qPCR</td> </tr><tr><td><a href="https://www.mdpi.com/1424-8247/16/10/1439">The development of a smart magnetic resonance imaging and chemical exchange saturation transfer contrast agent for the imaging of sulfatase activity</a></td> <td>NA (proprietary ligand linked to gadolinium)</td> <td>Imaging enzyme activity</td> <td>fast field cycling NMR relaxometry, z-spectrum</td> </tr><tr><td><a href="https://pubmed.ncbi.nlm.nih.gov/37976153/">Quantification of cell death and proliferation of patient-derived ovarian cancer organoids through 3D imaging and image analysis</a></td> <td>patient-derived ovarian cancer organoids</td> <td>Drug screening</td> <td>high content imaging and analysis</td> </tr><tr><td><a href="https://pubmed.ncbi.nlm.nih.gov/38172668/">A new physiological medium uncovers biochemical and cellular alterations in Lesch-Nyhan disease fibroblasts</a></td> <td>primary human skin fibroblasts from healthy individuals and those with Lesch-Nyhan disease</td> <td>Disease biology</td> <td>scratch assay, qPCR, mitochondrial respiration</td> </tr><tr><td><a href="https://pubmed.ncbi.nlm.nih.gov/38452090/">Vitamin A resolves lineage plasticity to orchestrate stem cell lineage choices</a></td> <td>mouse hair follicle stem cells</td> <td>Stem cell differentiation</td> <td>ATAC-seq, RNA-seq, CUT&amp;RUN (CNR)</td> </tr><tr><td><a href="https://pubmed.ncbi.nlm.nih.gov/38771036/">Human plasma-like medium (HPLM) induces Cryptococcus neoformans in vivo cell morphologies</a></td> <td>Cryptococcus neoformans (C. neoformans)</td> <td> Host-pathogen interaction</td> <td>flow cytometry</td> </tr><tr><td><a href="https://pubmed.ncbi.nlm.nih.gov/38977907/">CRISPR-based functional profiling of the Toxoplasma gondii genome during acute murine infection</a></td> <td>toxoplasma gondii</td> <td>Host-pathogen interaction</td> <td>genome wide gene survey</td> </tr><tr><td><a href="https://pubmed.ncbi.nlm.nih.gov/39299621/">Engineered myovascular 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