{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T11:59:44Z","timestamp":1790769584136,"version":"4.1.0"},"reference-count":62,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sig Transduct Target Ther"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Current therapies for type 1 diabetes mellitus (T1DM) rarely halt progressive \u03b2-cell function loss due to autoimmune attack. Human gingiva-derived mesenchymal stem cells (GMSCs) have been shown to have therapeutic effects on a variety of autoimmune diseases through their potent immunomodulatory capacity, but clinical evidence for these effects is lacking in patients with T1DM. Here, we performed a double-blind, randomized, placebo-controlled, phase 1 trial to evaluate the safety and efficacy of GMSC therapy in T1DM patients (ChiCTR1800018339). Patients received 4 intravenous injections of GMSCs (1.0\u2009\u00d7\u200910\n                    <jats:sup>6<\/jats:sup>\n                    \/kg) or placebo at intervals of 3 weeks between each treatment in combination with routine insulin therapy during the entire trial. All 18 randomized patients completed the trial. At week 12, patients receiving GMSCs displayed improvements in residual \u03b2-cell function, as evaluated by C-peptide levels, along with a decrease in the requirement for daily insulin treatment. Remarkably, one patient who received GMSC therapy achieved insulin withdrawal after the first treatment. Moreover, both groups had equal glycemic control, and GMSC therapy was not associated with an increased risk of adverse events, including hypoglycemia. Mechanistically, peripheral exhausted CD8\n                    <jats:sup>+<\/jats:sup>\n                    T-cell proportions were significantly increased, which is consistent with the results of single-cell sequencing and in vivo and in vitro experiments, suggesting that GMSCs potentially induce CD8\n                    <jats:sup>+<\/jats:sup>\n                    T-cell exhaustion to alleviate \u03b2-cell autoimmune injury. Overall, this study is the first clinical trial evaluating the safety and therapeutic effect of GMSC therapy in T1DM patients, indicating that GMSCs might serve as a promising novel treatment option for T1DM.\n                  <\/jats:p>","DOI":"10.1038\/s41392-026-03021-8","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T11:18:48Z","timestamp":1790767128000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Safety and efficacy of human gingiva-derived mesenchymal stem cells in patients with type 1 diabetes: a double-blind, randomized, placebo-controlled, phase 1 trial"],"prefix":"10.1038","volume":"11","author":[{"given":"Qi","family":"Tang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liwen","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xixiang","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donglan","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhua","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengyin","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5611-4774","authenticated-orcid":false,"given":"Song Guo","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanming","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,30]]},"reference":[{"key":"3021_CR1","doi-asserted-by":"publisher","first-page":"1486","DOI":"10.2337\/dc18-0465","volume":"41","author":"BM Shields","year":"2018","unstructured":"Shields, B. 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