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While primary islets, the gold standard for in vitro models, have a short culture life of approximately 1\u20132 weeks, we developed a novel protocol that employs reformed islets following dispersion coupled with a fine-tuned culture environment. Reformed islets exhibit physiological characteristics similar to primary islets, enabling high-resolution imaging and repeated functional assessment. Unlike other in vitro platforms, reformed islets retain an immune population, allowing the study of interactions between \u03b2 cells and resident and infiltrating immune cells. Analyses showed that reformed islets have a similar composition and cytoarchitecture to primary islets, including macrophages and T cells, and can secrete insulin in response to glucose. Reformed islets exhibited partial dedifferentiation compared to native islets but were otherwise transcriptionally similar. The reformed islets offer a useful platform for studying diabetes pathology and can recapitulate both T1DM and T2DM disease milieus, providing an advantage over other models, such as mouse and human \u03b2-cell lines, which lack the input of non-\u03b2-endocrine cells and immune cell crosstalk.<\/jats:p>","DOI":"10.1038\/s41420-024-02234-6","type":"journal-article","created":{"date-parts":[[2024,11,23]],"date-time":"2024-11-23T14:29:18Z","timestamp":1732372158000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Reformed islets: a long-term primary cell platform for exploring mouse and human islet biology"],"prefix":"10.1038","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1887-5449","authenticated-orcid":false,"given":"N.","family":"Haq","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. 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All human islets were retrieved from non-diabetic, heart-beating, and brain-dead donors and isolated by cold collagenase digestion [\n                      \n                      ,\n                      \n                      ] in accordance with relevant guidelines and regulations with appropriate ethical approval from the King\u2019s College London Human Islet Research Tissue Bank (KCL HI-RTB; 20\/SW\/0074). An assent form was completed by a relative of the pancreas donor for all the islets used in the study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}}],"article-number":"480"}}