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However, several obstacles hinder the long\u2010term efficacy of this therapy. A major challenge is the scarcity of donor organs. During the isolation process, islets are disconnected from their extracellular matrix (ECM) and vasculature, leading to significant loss due to anoikis and hypoxia. Additionally, inflammatory and rejection reactions further compromise islet survival and engraftment success. Extensive efforts are being made to improve the efficacy of islet transplantation. These strategies include promoting revascularization and ECM support through bioengineering techniques, exploring alternative sources of insulin\u2010secreting cells, and providing immunomodulation for the graft. Despite these advancements, a significant gap remains in integrating these strategies into a cohesive approach that effectively replicates the native endocrine environment. Specifically, the lack of comprehensive methods to address both the structural and functional aspects of the endocrine niche limits reproducibility and clinical translation. Therefore, bioengineering an endocrine pancreas must aim to recreate the endocrine niche to achieve lifelong efficacy and insulin independence. This review discusses various strategies developed to produce the building blocks for generating a vascularized, immune\u2010protected insulin\u2010secreting construct, emphasizing the importance of the endocrine niche's composition and function.<\/jats:p>","DOI":"10.1111\/aor.14950","type":"journal-article","created":{"date-parts":[[2025,1,23]],"date-time":"2025-01-23T04:01:17Z","timestamp":1737604877000},"page":"541-555","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Recreating the Endocrine Niche: Advances in Bioengineering the Pancreas"],"prefix":"10.1111","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7221-9413","authenticated-orcid":false,"given":"Laura Mar","family":"Fonseca","sequence":"first","affiliation":[{"name":"Laboratory of Tissue Engineering and Organ Regeneration, Department of Surgery University of Geneva  Geneva Switzerland"},{"name":"Cell Isolation and Transplantation Center, Department of Surgery Geneva University Hospitals and University of Geneva  Geneva Switzerland"},{"name":"Faculty Diabetes Center University of Geneva Medical Center, University of Geneva  Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicerine","family":"Krause","sequence":"additional","affiliation":[{"name":"Laboratory of Tissue Engineering and Organ Regeneration, Department of Surgery University of Geneva  Geneva Switzerland"},{"name":"Cell Isolation and Transplantation Center, Department of Surgery Geneva University Hospitals and University of Geneva  Geneva Switzerland"},{"name":"Faculty Diabetes Center University of Geneva Medical Center, University of Geneva  Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3175-0205","authenticated-orcid":false,"given":"Fanny","family":"Lebreton","sequence":"additional","affiliation":[{"name":"Laboratory of Tissue Engineering and Organ Regeneration, Department of Surgery University of Geneva  Geneva Switzerland"},{"name":"Cell Isolation and Transplantation Center, Department of Surgery Geneva University Hospitals and University of Geneva  Geneva Switzerland"},{"name":"Faculty Diabetes Center University of Geneva Medical Center, University of Geneva  Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7969-1937","authenticated-orcid":false,"given":"Ekaterine","family":"Berishvili","sequence":"additional","affiliation":[{"name":"Laboratory of Tissue Engineering and Organ Regeneration, Department of Surgery University of Geneva  Geneva Switzerland"},{"name":"Cell Isolation and Transplantation Center, Department of Surgery Geneva University Hospitals and University of Geneva  Geneva Switzerland"},{"name":"Faculty Diabetes Center University of Geneva Medical Center, University of Geneva  Geneva Switzerland"},{"name":"Institute of Medical and Public Health Research Ilia State University  Tbilisi Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,1,23]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc25-S002"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc25-S009"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1159\/000542206"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lpm.2022.104139"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-022-05804-4"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(22)00114-0"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-18603-0_11"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells13211783"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1080\/15476278.2018.1517509"},{"key":"e_1_2_11_11_1","article-title":"The Pancreatic Islet: A Micro\u2010Organ in Control","volume":"9","author":"Abdulreda M. 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