{"id":27889,"date":"2020-08-19T00:00:37","date_gmt":"2020-08-19T07:00:37","guid":{"rendered":"https:\/\/vermont.salk.edu\/?post_type=disclosure&#038;p=27889"},"modified":"2024-01-30T14:39:46","modified_gmt":"2024-01-30T22:39:46","slug":"first-immune-evading-cells-created-to-treat-type-1-diabetes","status":"publish","type":"disclosure","link":"https:\/\/www.salk.edu\/es\/news-release\/first-immune-evading-cells-created-to-treat-type-1-diabetes\/","title":{"rendered":"First immune-evading cells created to treat type 1 diabetes"},"content":{"rendered":"<p>LA JOLLA\u2014Salk Institute scientists have made a major advance in the pursuit of a safe and effective treatment for type 1 diabetes, an illness that impacts an estimated 1.6 million Americans with a cost of $14.4 billion annually.<\/p>\n<p>Using stem cell technology, Salk researchers generated the first human insulin-producing pancreatic cell clusters able to evade the immune system, as detailed in the journal <a href=\"https:\/\/www.nature.com\/articles\/s41586-020-2631-z\" target=\"_blank\" rel=\"noopener noreferrer\"><em>Naturaleza<\/em><\/a> on August 19, 2020. These \u201cimmune shielded\u201d cell clusters controlled blood glucose without immunosuppressive drugs in mice, once transplanted in the body.<\/p>\n<div class=\"row\" style=\"\"><div class=\"col-md-12 col-md-push-0\"><div class=\"video-anchor\" id=\"video-hwZLKWWs5cs\"><\/div><div class=\"embed-responsive embed-responsive-16by9\"> <iframe class=\"embed-responsive-item\" src=\"\/\/www.youtube.com\/embed\/hwZLKWWs5cs?rel=0\" webkitallowfullscreen mozallowfullscreen allowfullscreen><\/iframe><\/div><!-- .embed-responsive --><\/div><!-- .col-md-*size --><\/div><!-- .\/row -->\n<p>\u201cMost type 1 diabetics are children and teenagers,\u201d says Salk Professor <a href=\"https:\/\/www.salk.edu\/es\/scientist\/ronald-evans\/\">Ronald Evans<\/a>, senior author and holder of the March of Dimes Chair in Molecular and Developmental Biology. \u201cThis is a disease that is historically hard to manage with drugs. We hope that regenerative medicine in combination with immune shielding can make a real difference in the field by replacing damaged cells with lab-generated human islet-like cell clusters that produce normal amounts of insulin on demand.\u201d<\/p>\n<p>Type 1 diabetes is a lifelong condition that is challenging to manage, even with automated devices that deliver insulin to regulate blood sugar. Transplants of pancreatic beta islets\u2014clusters of cells that make insulin and other hormones\u2014from donor tissue can provide a cure, but require patients to take life-long immunosuppressing drugs, which carry serious risks. For decades, researchers have sought a better way to replenish lost pancreatic cells. Now, device-free transplantation of insulin-producing cells like these brings us a step closer to curing the disease, according to the lab.<\/p>\n<figure id=\"attachment_27915\"  class=\"wp-caption alignright\"><img loading=\"lazy\" decoding=\"async\" width=\"458\" height=\"342\" class=\"img-responsive wp-image-27915 size-col-md-5\" src=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2020\/08\/HILO-GFP06142020-458x342.jpg\" alt=\"Shown here, human islet-like organoids express insulin, which is indicated by the green color.\" srcset=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2020\/08\/HILO-GFP06142020-458x342.jpg 458w, https:\/\/www.salk.edu\/wp-content\/uploads\/2020\/08\/HILO-GFP06142020-300x224.jpg 300w, https:\/\/www.salk.edu\/wp-content\/uploads\/2020\/08\/HILO-GFP06142020-1024x765.jpg 1024w, https:\/\/www.salk.edu\/wp-content\/uploads\/2020\/08\/HILO-GFP06142020-768x574.jpg 768w, https:\/\/www.salk.edu\/wp-content\/uploads\/2020\/08\/HILO-GFP06142020-147x110.jpg 147w, https:\/\/www.salk.edu\/wp-content\/uploads\/2020\/08\/HILO-GFP06142020-585x437.jpg 585w, https:\/\/www.salk.edu\/wp-content\/uploads\/2020\/08\/HILO-GFP06142020-553x413.jpg 553w, https:\/\/www.salk.edu\/wp-content\/uploads\/2020\/08\/HILO-GFP06142020-750x560.jpg 750w, https:\/\/www.salk.edu\/wp-content\/uploads\/2020\/08\/HILO-GFP06142020-767x573.jpg 767w, https:\/\/www.salk.edu\/wp-content\/uploads\/2020\/08\/HILO-GFP06142020-945x706.jpg 945w, https:\/\/www.salk.edu\/wp-content\/uploads\/2020\/08\/HILO-GFP06142020-1250x934.jpg 1250w, https:\/\/www.salk.edu\/wp-content\/uploads\/2020\/08\/HILO-GFP06142020-400x299.jpg 400w, https:\/\/www.salk.edu\/wp-content\/uploads\/2020\/08\/HILO-GFP06142020.jpg 1392w\" sizes=\"auto, (max-width: 458px) 100vw, 458px\" \/><figcaption class=\"wp-caption-text\">Shown here, human islet-like organoids express insulin, which is indicated by the green color.<\/p>\n<p><a href=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2020\/08\/HILO-GFP06142020.jpg\">Haga clic aqu\u00ed<\/a> para obtener una imagen en alta resoluci\u00f3n.<\/p>\n<p>Cr\u00e9dito: Instituto Salk<\/figcaption><\/figure>\n<p>In a <a href=\"https:\/\/www.salk.edu\/es\/news-release\/salk-scientists-find-secret-sauce-for-personalized-functional-insulin-producing-cells\/\">previous study<\/a>, the Evans lab overcame an impediment in the field, in which stem-cell-derived beta-like cells produced insulin, but were not functional. The cells did not release insulin in response to glucose, as they were simply under powered, according to Evans. His team discovered a genetic switch called ERR-gamma that when flipped, \u201cturbo-charges\u201d the cells.<\/p>\n<p>\u201cWhen we add ERR-gamma, the cells have the energy they need to do their job,\u201d says Michael Downes, a Salk senior staff scientist and co-author of both studies. \u201cThese cells are healthy and robust and can deliver insulin when they sense high glucose levels.\u201d<\/p>\n<p>A critical part of the new study was to develop a way to grow beta-like cells in a three-dimensional environment that approximates the human pancreas. This gave the cells an islet-like property. Importantly, the team discovered that a protein called WNT4 was able to turn on the ERR-gamma-driven maturation switch. This combination of steps generated functional cell clusters that mimic human islets: so-called human islet-like organoids (HILOs).<\/p>\n<p>Next the team tackled the complex issue of immune rejection. Normal tissue transplants require lifelong immune-suppressive therapies to protect the tissue from being attacked by the immune system; however these therapies also increase the risk for infections. Inspired by the successes of immunotherapy drugs for cancer, the team initially showed that the checkpoint protein PD-L1 protected the transplanted cells. \u201cBy expressing PD-L1, which acts as an immune blocker, the transplanted organoids are able to hide from the immune system,\u201d says first author Eiji Yoshihara, a former staff scientist in the lab.<\/p>\n<figure id=\"attachment_27916\"  class=\"wp-caption alignleft\"><img loading=\"lazy\" decoding=\"async\" width=\"458\" height=\"154\" class=\"img-responsive wp-image-27916 size-col-md-5\" src=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2020\/08\/Evans-Nature-Diabetes-Salk-PR-458x154.jpg\" alt=\"From left: Michael Downes, Eiji Yoshihara and Ronald Evans.\" srcset=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2020\/08\/Evans-Nature-Diabetes-Salk-PR-458x154.jpg 458w, https:\/\/www.salk.edu\/wp-content\/uploads\/2020\/08\/Evans-Nature-Diabetes-Salk-PR-300x101.jpg 300w, https:\/\/www.salk.edu\/wp-content\/uploads\/2020\/08\/Evans-Nature-Diabetes-Salk-PR-147x49.jpg 147w, https:\/\/www.salk.edu\/wp-content\/uploads\/2020\/08\/Evans-Nature-Diabetes-Salk-PR-585x196.jpg 585w, https:\/\/www.salk.edu\/wp-content\/uploads\/2020\/08\/Evans-Nature-Diabetes-Salk-PR-553x186.jpg 553w, https:\/\/www.salk.edu\/wp-content\/uploads\/2020\/08\/Evans-Nature-Diabetes-Salk-PR-750x252.jpg 750w, https:\/\/www.salk.edu\/wp-content\/uploads\/2020\/08\/Evans-Nature-Diabetes-Salk-PR-400x134.jpg 400w, https:\/\/www.salk.edu\/wp-content\/uploads\/2020\/08\/Evans-Nature-Diabetes-Salk-PR.jpg 763w\" sizes=\"auto, (max-width: 458px) 100vw, 458px\" \/><figcaption class=\"wp-caption-text\">From left: Michael Downes, Eiji Yoshihara and Ronald Evans.<\/p>\n<p><a href=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2020\/08\/Evans-Nature-Diabetes-Salk-PR.jpg\">Haga clic aqu\u00ed<\/a> para obtener una imagen en alta resoluci\u00f3n.<\/p>\n<p>Cr\u00e9dito: Instituto Salk<\/figcaption><\/figure>\n<p>Yoshihara then developed a method to induce PD-L1 in HILOs with short pulses of the protein interferon gamma. When transplanted into diabetic mice, these immune-evasive HILOs provided sustained blood glucose control in diabetic mice with healthy immune systems.<\/p>\n<p>\u201cThis is the first study to show that you can protect HILOs from the immune system without genetic manipulation,\u201d Downes explains. \u201cIf we are able to develop this as a therapy, patients will not need to take immune-suppressing drugs.\u201d<\/p>\n<p>More research needs to be done before this system can be advanced to clinical trials. The transplanted organoids need to be tested in mice for longer periods of time to confirm that their effects are long-lasting. More work needs to be done to ensure they would be safe to use in humans as well. \u201cWe now have a product that could potentially be used in patients without requiring any kind of device,\u201d Evans concludes.<\/p>\n<p>Other researchers on the paper were Carolyn O\u2019Connor, Emanuel Gasser, Zong Wei, Tae Gyu Oh, Tiffany W. Tseng, Dan Wang, Fritz Cayabyab, Yang Dai, Ruth T. Yu, and Annette R. Atkins of Salk and Christopher Liddle of the Westmead Institute for Medical Research and Sydney Medical School in Australia.<\/p>\n<p>This work was supported by grants from California Institute of Regenerative Medicine grant DISC2-11175, National Institutes of Health grant 1RO1DK120480-01, the Leona M. and Harry B. Helmsley Charitable Trust, to Evans. Liddle and Downes were funded by grants from the National Health and Medical Research Council of Australia Project. Yoshihara was supported by a DRC P&amp;F grant. Thank you also\u00a0to\u00a0Steven and Lisa Altman\u00a0for supporting the lab.<\/p>\n<p><strong>DOI:<\/strong> 10.1038\/s41586-020-2631-z<\/p>\n<p><strong>For an FAQ about this work, <a href=\"https:\/\/www.salk.edu\/es\/news\/salk-news\/salk-institute-evans-lab-diabetes-research-faq\/\" target=\"_blank\" rel=\"noopener noreferrer\">haz clic aqu\u00ed<\/a>.<\/strong><\/p>","protected":false},"featured_media":27915,"template":"","faculty":[91],"disease-research":[173,146,123],"class_list":["post-27889","disclosure","type-disclosure","status-publish","has-post-thumbnail","hentry","faculty-ronald-evans","disease-research-diabetes-type-1","disease-research-aging-and-regenerative-medicine","disease-research-metabolism-and-diabetes"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.3 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>First immune-evading cells created to treat type 1 diabetes - Salk Institute for Biological Studies<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.salk.edu\/es\/news-release\/first-immune-evading-cells-created-to-treat-type-1-diabetes\/\" \/>\n<meta property=\"og:locale\" content=\"es_MX\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"First immune-evading cells created to treat type 1 diabetes - 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