{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T14:57:43Z","timestamp":1786114663805,"version":"build-2736575974"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":16,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Guizhou Provincial Health Commission Science and Technology Fund Project","award":["gzwkj2025-300"],"award-info":[{"award-number":["gzwkj2025-300"]}]},{"name":"West China Hospital of Sichuan University","award":["ZYYC24002"],"award-info":[{"award-number":["ZYYC24002"]}]},{"DOI":"10.13039\/501100001809","name":"Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82370645"],"award-info":[{"award-number":["82370645"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82270643"],"award-info":[{"award-number":["82270643"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82170621"],"award-info":[{"award-number":["82170621"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82070644"],"award-info":[{"award-number":["82070644"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013365","name":"West China Hospital, Sichuan University","doi-asserted-by":"publisher","award":["ZYGD22006"],"award-info":[{"award-number":["ZYGD22006"]}],"id":[{"id":"10.13039\/501100013365","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by the destruction of pancreatic \u03b2 cells, leading to lifelong insulin dependence and an increased risk of severe complications. Three-dimensional stem cells (3D SCs) culture systems have emerged as a superior alternative by more accurately mimicking the in vivo microenvironment and enhancing stemness maintenance, regenerative efficiency, and paracrine secretion. However, studies exploring the application of 3D SCs in T1D remain limited. Here, we developed a novel serum- and cytokine-free orbital-shaking system. It enables efficient and large-scale reprogramming of somatic cells into 3D embryonic-like stem cell spheroids (Sph-Es) characterized by robust pluripotency and improved safety. To enhance therapeutic utility, Sph-Es were irradiated and transduced with INS-expressing adenoviral vectors to generate Sph-R-Ins, allowing transient insulin production without permanent genomic modification. In STZ-induced T1D mice, Sph-R-Ins improved glycemic control and glucose tolerance and increased mouse insulin and C-peptide responses, indicating improved endogenous islet function. Donor-cell tracking analyses showed no pancreatic engraftment, supporting an indirect mode of action. Additional transcriptomic, immunological, and ex vivo studies indicated that the therapeutic benefit was accompanied by ECM-related signaling changes, reduced inflammatory infiltration, enhanced M2 macrophage polarization and Treg-associated immune regulation, improved metabolic signaling, and spheroid-derived paracrine support of islet function. Together, these findings establish a mechanically guided 3D stem cell\u2013gene therapy platform with both endocrine and immunometabolic benefits in T1D.<\/jats:p>","DOI":"10.1093\/stcltm\/szag054","type":"journal-article","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T12:04:25Z","timestamp":1778760265000},"source":"Crossref","is-referenced-by-count":0,"title":["Insulin gene-modified 3D stem cells for enhanced islet regeneration and systemic reversal of type 1 diabetes"],"prefix":"10.1093","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9623-2716","authenticated-orcid":false,"given":"Qian","family":"Li","sequence":"first","affiliation":[{"name":"Division of Liver Surgery, Department of General Surgery and Laboratory of Liver Surgery, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University , Chengdu 610041,","place":["China"]},{"name":"Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University , Chengdu 610041,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Ma","sequence":"additional","affiliation":[{"name":"Division of Liver Surgery, Department of General Surgery and Laboratory of Liver Surgery, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University , Chengdu 610041,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kefei","family":"Yuan","sequence":"additional","affiliation":[{"name":"Division of Liver Surgery, Department of General Surgery and Laboratory of Liver Surgery, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University , Chengdu 610041,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxin","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Liver Surgery, Department of General Surgery and Laboratory of Liver Surgery, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University , Chengdu 610041,","place":["China"]},{"name":"Department of General Surgery, Dafang County People\u2019s Hospital , Bijie, Guizhou Province 551600,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Fu","sequence":"additional","affiliation":[{"name":"Division of Liver Surgery, Department of General Surgery and Laboratory of Liver Surgery, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University , Chengdu 610041,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanxi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University , Chengdu 610041,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianchuan","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University , Chengdu 610041,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangzheng","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Liver Surgery, Department of General Surgery and Laboratory of Liver Surgery, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University , Chengdu 610041,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanna","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Blood Transfusion, Sichuan Provincial People\u2019s Hospital, University of Electronic Science and Technology of China , Chengdu, Sichuan 610072,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiancheng","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University , Chengdu 610041,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Zeng","sequence":"additional","affiliation":[{"name":"Division of Liver Surgery, Department of General Surgery and Laboratory of Liver Surgery, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University , Chengdu 610041,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Liver Surgery, Department of General Surgery and Laboratory of Liver Surgery, and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University , Chengdu 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