{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,9]],"date-time":"2026-11-09T21:02:00Z","timestamp":1794258120303,"version":"4.9.0"},"reference-count":41,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T00:00:00Z","timestamp":1762128000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T00:00:00Z","timestamp":1762128000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"National Key Research and Development Program of China","award":["2023YFF1000904"],"award-info":[{"award-number":["2023YFF1000904"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32372970"],"award-info":[{"award-number":["32372970"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Stem Cell Res Ther"],"abstract":"Abstract<\/jats:title>\n \n Introduction<\/jats:title>\n \n Type 1 diabetes (T1D) results from the destruction of pancreatic \u03b2-cells, leading to insulin deficiency. As insulin therapy does not affect disease progression, advancements in immune regulation therapies have emerged, including the reconstitution of the insulin secretory system. Cysteine-rich acidic secretory protein (\n SPARC<\/jats:italic>\n ) is an extracellular matrix glycoprotein that regulates cell adhesion, facilitating cell migration, and mediating interactions between cells and their extracellular matrix.\n SPARC<\/jats:italic>\n is overexpressed during tissue repair and is involved in \u03b2-cells survival. However, the potential of\n SPARC<\/jats:italic>\n -modified mesenchymal stem cells (MSCs) to improve insulin secretion has not been thoroughly investigated. This study investigated the therapeutic effects of\n SPARC<\/jats:italic>\n -MSCs in vivo and in vitro and assessed whether\n SPARC<\/jats:italic>\n enhances survival and insulin secretion after \u03b2-cells injury.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n In vivo, we established T1D models in mice and canine using\n SPARC<\/jats:italic>\n -MSCs for cell transplantation. In vitro, MIN6 cells were damaged with STZ, and\n SPARC<\/jats:italic>\n -MSC supernatant was co-cultured with MIN6 for various assays.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Our study demonstrated that\n SPARC<\/jats:italic>\n enhanced the regenerative capacity and migratory efficiency of MSCs after H\n 2<\/jats:sub>\n O\n 2<\/jats:sub>\n injury and improved their morphology. In STZ-induced canine and mice diabetes models,\n SPARC<\/jats:italic>\n -MSCs therapy significantly reduced hyperglycemia, improved oral glucose tolerance test (OGTT), and reversed weight loss in canine. Biochemical analyses showed improved liver function, and histological examination revealed restored islet area was significantly restored. Transcriptome and proteome sequencing indicated significant enrichment in calcium binding and cell migration pathways. Co-culturing\n SPARC<\/jats:italic>\n -MSC supernatant with MIN6 cells after STZ injury restored their regenerative ability, enhancing insulin secretion and ATP content under high glucose stimulation.\n SPARC<\/jats:italic>\n treatment also significantly increased intracellular Ca\n 2+<\/jats:sup>\n levels in MIN6 cells.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n SPARC<\/jats:italic>\n significantly promotes cell regeneration and stimulates insulin secretion by increasing intracellular ATP and Ca\n 2+<\/jats:sup>\n influx. In diabetic canine and mice models, it alleviated hyperglycemia, improved glucose tolerance, and enhanced pancreatic islet area and insulin secretion.\n <\/jats:p>\n <\/jats:sec>\n \n Graphical Abstract<\/jats:title>\n <\/jats:sec>","DOI":"10.1186\/s13287-025-04727-2","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T09:40:35Z","timestamp":1762162835000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["SPARC-modified mesenchymal stem cells promote recovery of \u03b2-cells and insulin secretion by calcium ion homeostasis"],"prefix":"10.1186","volume":"16","author":[{"given":"Jiaqi","family":"Gao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Balun","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongkai","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenchen","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikita","family":"Merzlikin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongyao","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixi","family":"Ling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zengyu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenlong","family":"zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianqi","family":"Dai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lydmila","family":"Gerunova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changrong","family":"Lv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9788-8592","authenticated-orcid":false,"given":"Jinlian","family":"Hua","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,3]]},"reference":[{"key":"4727_CR1","doi-asserted-by":"publisher","first-page":"62","DOI":"10.2337\/dc11-S062","volume":"34","author":"Diagnosis and classification of diabetes mellitus","year":"2011","unstructured":"Diagnosis and classification of diabetes mellitus. 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Diabetes Metab J. 2019;43(1):3.","journal-title":"Diabetes Metab J"}],"container-title":["Stem Cell Research & Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13287-025-04727-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13287-025-04727-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13287-025-04727-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T11:08:01Z","timestamp":1762168081000},"score":1,"resource":{"primary":{"URL":"https:\/\/stemcellres.biomedcentral.com\/articles\/10.1186\/s13287-025-04727-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,3]]},"references-count":41,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["4727"],"URL":"https:\/\/doi.org\/10.1186\/s13287-025-04727-2","relation":{},"ISSN":["1757-6512"],"issn-type":[{"value":"1757-6512","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,3]]},"assertion":[{"value":"28 February 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 October 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 November 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study of \u201c\n SPARC\n -modified Mesenchymal Stem Cells Promote Recovery of \u03b2-cells and Insulin Secretion by Calcium Ion Homeostasis\u201d was approved by the Northwest A&F University Animal Care and Use Ethics Committee on Nov.09, 2024, with approval number IACUC 2024-1109. The study of \u201cEstablish of MSCs and SPARC-MSCs\u201d was approved by the Northwest A&F University Animal Care and Use Ethics Committee on Feb.20, 2023, with approval number NWAFU.No20234580d0600601.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"607"}}