{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T13:10:58Z","timestamp":1777468258943,"version":"3.51.4"},"reference-count":56,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T00:00:00Z","timestamp":1749513600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["CIHR MOP# 378189"],"award-info":[{"award-number":["CIHR MOP# 378189"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,8,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Residual beta cell function has been documented in \u201cmedalist\u201d patients who have lived with Type 1 diabetes (T1D) for &amp;gt;50 years. In addition, endocrine cell neogenesis first occurs in the developing human embryo from progenitor cells derived from pancreatic ductal epithelial structure. Thus, beta cell conversion from a dormant epithelial precursor remains a promising approach to regenerate islets during T1D. We have previously shown that intra-pancreatic (iPan) injection of Wnt pathway-stimulated conditioned media (Wnt+\u2005CdM) generated from human bone marrow-derived multipotent stromal cells (MSC) contained islet regenerative factors that reduced hyperglycemia and recovered beta cell mass in streptozotocin-treated mice. However, the endogenous source of regenerated beta cells remains unknown. Herein, we employed cytokeratin 19 (CK19)-CreERT Rosa26-mTomato lineage-tracing mice to assess the endocrine conversion of CK19+\u2005cells during MSC CdM-induced islet regeneration. Mice iPan-injected with Wnt+\u2005CdM demonstrated reduced blood glucose levels and improved glucose tolerance compared to mice injected with unconditioned basal media. CdM-injected mice also showed increased islet number and beta cell mass, as well as CK19+\u2005cells within regenerating islets. The frequency of insulin\u2005+\u2005cells that co-expressed tdTomato within dissociated pancreas samples observed via flow cytometry was 5-fold higher in Wnt+\u2005CdM-injected mice (~5%) compared to basal media-injected controls (~1%). Collectively, in vivo lineage tracing revealed conversion of CK19+\u2005cells to functional beta cells partially contributed to islet regeneration induced by Wnt-activated MSC CdM. Future studies are required to delineate alternate cell types and mechanisms participating in islet regeneration induced by direct delivery of MSC-CdM.<\/jats:p>","DOI":"10.1093\/stmcls\/sxaf036","type":"journal-article","created":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T02:58:55Z","timestamp":1749524335000},"source":"Crossref","is-referenced-by-count":3,"title":["Contribution of cytokeratin 19-expressing cells towards islet regeneration induced by multipotent stromal cell secreted proteins"],"prefix":"10.1093","volume":"43","author":[{"given":"Nazihah","family":"Rasiwala","sequence":"first","affiliation":[{"name":"Department of Physiology and Pharmacology, Western University , London, ON N6A 3K7 ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gillian I","family":"Bell","sequence":"additional","affiliation":[{"name":"Molecular Medicine Research Laboratories, Robarts Research Institute , London, ON N6A 5B7 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