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Type I diabetes mellitus results in insulin-deficient hyperglycemia, causing serious health issues. Pancreatic islet transplantation is a promising way to treat type I diabetes. It remains a challenge to obtain the islet spheroid with a core\u2013mantle architecture similar to that of rodent pancreatic islets in vivo. We demonstrate a methodology to produce islet spheroids composed of \u03b2 and \u03b1 cells with a core\u2013mantle architecture based on the magneto-Archimedes effect in a high-throughput manner. The core\u2013mantle islet spheroid (CMIS) shows a more sensitive glucose stimulation response and better insulin secretion performance than the mixed islet spheroid at high-glucose conditions, as indicated by the relative mRNA expression levels. The high-throughput toxicity tests on immunosuppressive drugs using CMIS (\u03b2:\u03b1 = 7:3) indicate that mycophenolate mofetil exhibits a less negative effect on cell viability and insulin secretion than rapamycin and tacrolimus. The CMIS (\u03b2:\u03b1 = 7:3) exhibits a better therapeutic effect in treating diabetic mice after transplantation than the other types of islet spheroids, which holds great potential in the clinical treatment of diabetes. The proposed versatile methodology for core\u2013mantle islet spheroids paves the path for fabricating spatially coded tissues with a complicated architecture in the organoid field.<\/jats:p>","DOI":"10.1021\/acsami.6c07368","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T19:51:38Z","timestamp":1788292298000},"page":"47326-47338","source":"Crossref","is-referenced-by-count":0,"title":["High-Throughput Production of Pancreatic Islet Spheroids with a Core\u2013Mantle Architecture for the Treatment of Type I Diabetes in Mice"],"prefix":"10.1021","volume":"18","author":[{"given":"Xiangxiang","family":"Zhang","sequence":"first","affiliation":[{"name":"Harbin Institute of Technology , , 92 West Da-Zhi Street , ,","place":["Harbin, China, 150001"]},{"name":"Peking University First Hospital , , ,","place":["Beijing, China, 100034"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Zhao","sequence":"additional","affiliation":[{"name":"Harbin Institute of Technology , , 92 West Da-Zhi Street , ,","place":["Harbin, China, 150001"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Li","sequence":"additional","affiliation":[{"name":"Harbin Institute of Technology , , 92 West Da-Zhi Street , ,","place":["Harbin, China, 150001"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shubin","family":"Li","sequence":"additional","affiliation":[{"name":"Harbin Institute of Technology , , 92 West Da-Zhi Street , ,","place":["Harbin, China, 150001"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuefeng","family":"Tang","sequence":"additional","affiliation":[{"name":"Harbin Institute of Technology , , 92 West Da-Zhi Street , ,","place":["Harbin, China, 150001"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Harbin Institute of Technology , , 92 West Da-Zhi Street , ,","place":["Harbin, China, 150001"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fukai","family":"Liu","sequence":"additional","affiliation":[{"name":"First Affiliated Hospital of Harbin Medical University , , 23 You Zheng Street , ,","place":["Harbin, China, 150001"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8571-6187","authenticated-orcid":true,"given":"Xiaojun","family":"Han","sequence":"additional","affiliation":[{"name":"Harbin Institute of Technology , , 92 West Da-Zhi Street , ,","place":["Harbin, China, 150001"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,27]]},"reference":[{"key":"2026091516065999500_cit1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2017.17","article-title":"Type 1 diabetes mellitus","volume":"3","author":"Atkinson","year":"2017","journal-title":"Nat. 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