{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T10:59:41Z","timestamp":1791197981087,"version":"4.1.0"},"reference-count":67,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>Beta-cell replacement aims to restore endogenous, glucose-responsive insulin secretion in type 1 diabetes. Donor-islet transplantation has shown that this approach can improve glycaemic control and prevent severe hypoglycaemia. Its wider use is limited by donor supply, early graft loss and chronic systemic immunosuppression. Pluripotent stem cells provide a renewable source of pancreatic progenitors and differentiated islet products. Recent clinical studies have reported C-peptide secretion and insulin independence in some recipients. However, cell supply is only one part of the problem. Product maturity, graft composition, implantation site, vascular support, immune injury and manufacturing quality all affect outcome. This review examines these factors as parts of one treatment system. It compares donor islets, stem-cell-derived products and islet-like organoids, then evaluates delivery and immune-protection strategies. It also considers clinical endpoints, patient selection and safety. We define functional cure as durable endogenous insulin secretion with physiological benefit at an acceptable total treatment burden. Current evidence provides early evidence of clinical activity and, in selected recipients, clinically meaningful efficacy. However, the available studies involve highly selected participants, small cohorts and\/or systemic immunosuppression. No platform has yet combined durable function, immune control, scalable production and acceptable long-term safety.<\/jats:p>","DOI":"10.3389\/fendo.2026.1981945","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T10:08:41Z","timestamp":1791194921000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Beta-cell replacement for type 1 diabetes: integrating cell products, engraftment and immune protection"],"prefix":"10.3389","volume":"17","author":[{"given":"Lan","family":"Chen","sequence":"first","affiliation":[{"name":"The Third Hospital Affiliated to Zhejiang Chinese Medical University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinhao","family":"Hu","sequence":"additional","affiliation":[{"name":"Zhejiang Chinese Medical University","place":["Hangzhou, 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