{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T12:41:03Z","timestamp":1791895263265,"version":"4.3.4"},"reference-count":71,"publisher":"American Diabetes Association","issue":"7","license":[{"start":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T00:00:00Z","timestamp":1745452800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/journals\/pages\/license"}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,7,1]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>Islet cell replacement therapies have evolved as a viable treatment option for type 1 diabetes complicated by problematic hypoglycemia and glycemic lability. Refinements of islet manufacturing, islet transplantation procedures, peritransplant recipient management, and immunosuppressive protocols allowed most recipients to achieve favorable outcomes. Subsequent phase 3 trials of transplantation of deceased donor islets documented the effectiveness of transplanted islets in restoring near-normoglycemia, glycemic stability, and protection from severe hypoglycemia, with an acceptable safety profile for the enrolled high-risk population. Health authorities in several countries have approved deceased donor islet transplantation for treating patients with type 1 diabetes and recurrent severe hypoglycemia. These achievements amplified academic and industry efforts to generate pluripotent stem cell\u2013derived \u03b2-cells through directed differentiation for \u03b2-cell replacement. Preliminary results of ongoing clinical trials suggest that the transplantation of stem cell\u2013derived \u03b2-cells can consistently restore insulin independence in immunosuppressed recipients with type 1 diabetes, thus signaling the profound progress made in generating an unlimited and a uniform supply of cells for transplant. Avoiding the risks of chronic immunosuppression represents the next frontier. Several strategies have entered or are approaching clinical investigation, including immune-isolating islets, engineering immune-privileged islet implantation sites, rendering islets immune evasive, and inducing immune tolerance in transplanted islets. Capitalizing on high-dimensional, multiomic technologies for deep profiling of graft-directed immunity and the fate of the graft will provide new insights that promise to translate into sustaining functional graft survival long-term. Leveraging these parallel progression paths will facilitate the wider clinical adoption of cell replacement therapies in diabetes care.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Article Highlights<\/jats:title>\n                    <jats:p>Transplantation of deceased donor\u2013derived primary human islets has restored near-normoglycemia and protection from severe hypoglycemia in immunosuppressed recipients with type 1 diabetes. Transplantation of embryonic stem cell\u2013derived \u03b2-cells has restored insulin independence\u00a0in immunosuppressed recipients with type 1 diabetes. Clinical trials are underway and planned to evaluate the safety and efficacy of transplantation of mature stem cell\u2013derived \u03b2-cells with transient, local, minimal, and\/or no-maintenance immunosuppression in recipients with type 1 diabetes. The high-dimensional, multiomic monitoring of immunity to transplanted islets and of the fate of the islet graft will faciliate the identification of determinants of sustained islet graft function and of patients most likely to benefit from cell replacement therapies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2337\/db25-0037","type":"journal-article","created":{"date-parts":[[2025,5,7]],"date-time":"2025-05-07T11:59:07Z","timestamp":1746619147000},"page":"1068-1077","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":50,"title":["Advances in Cell Replacement Therapies for Diabetes"],"prefix":"10.2337","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5962-7284","authenticated-orcid":false,"given":"Bernhard J.","family":"Hering","sequence":"first","affiliation":[{"name":"Department of Surgery, Schulze Diabetes Institute, University of Minnesota Medical School 1 , Minneapolis, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9253-838X","authenticated-orcid":false,"given":"Michael R.","family":"Rickels","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes & Metabolism, Department of Medicine, and Institute for Diabetes, Obesity & Metabolism, Perelman School of Medicine, University of Pennsylvania 2 , Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7324-4837","authenticated-orcid":false,"given":"Melena D.","family":"Bellin","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Pediatrics, University of Minnesota Medical School 3 , Minneapolis, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0426-3492","authenticated-orcid":false,"given":"Jeffrey R.","family":"Millman","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Metabolism and Lipid Research, Washington University School of Medicine 4 , St. Louis, MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice A.","family":"Tomei","sequence":"additional","affiliation":[{"name":"Diabetes Research Institute, Miller School of Medicine, University of Miami 5 , Miami, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6602-2518","authenticated-orcid":false,"given":"Andr\u00e9s J.","family":"Garc\u00eda","sequence":"additional","affiliation":[{"name":"George W. Woodruff School of Mechanical Engineering and Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology 6 , Atlanta, GA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haval","family":"Shirwan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Ellis Fischel Cancer Center, University of Missouri School of Medicine 7 , Columbia, MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0573-0646","authenticated-orcid":false,"given":"Cherie L.","family":"Stabler","sequence":"additional","affiliation":[{"name":"J. Crayton Pruitt Family Department of Biomedical Engineering, Herbert Wertheim College of Engineering, University of Florida 8 , Gainesville, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minglin","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Biological and Environmental Engineering, Cornell University 9 , Ithaca, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7830-4694","authenticated-orcid":false,"given":"Peng","family":"Yi","sequence":"additional","affiliation":[{"name":"Section for Islet Cell and Regenerative Biology, Joslin Diabetes Center 10 , Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xunrong","family":"Luo","sequence":"additional","affiliation":[{"name":"Duke Transplant Center, Duke University School of Medicine 11 , Durham, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qizhi","family":"Tang","sequence":"additional","affiliation":[{"name":"Diabetes Center, University of California 12 , San Francisco, San Francisco, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabarinathan","family":"Ramachandran","sequence":"additional","affiliation":[{"name":"Department of Surgery, Schulze Diabetes Institute, University of Minnesota Medical School 1 , Minneapolis, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose","family":"Oberholzer","sequence":"additional","affiliation":[{"name":"Department of Visceral Surgery and Transplantation, University Hospital Zurich 13 , Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camillo","family":"Ricordi","sequence":"additional","affiliation":[{"name":"Diabetes Research Institute, Miller School of Medicine, University of Miami 5 , Miami, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy J.","family":"Kieffer","sequence":"additional","affiliation":[{"name":"Department of Cellular and Physiological Sciences and Department of Surgery, Life Sciences Institute, and School of Biomedical Engineering, University of British Columbia, Vancouver 14 , British Columbia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6215-0990","authenticated-orcid":false,"given":"A.M. 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