{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T09:15:33Z","timestamp":1777626933871,"version":"3.51.4"},"reference-count":58,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"vor","delay-in-days":2,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["378189"],"award-info":[{"award-number":["378189"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Sheldon H. Weinstein Chair in Diabetes Research at the Schulich School of Medicine and Dentistry"},{"DOI":"10.13039\/501100004381","name":"Western University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004381","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Diabetes affects &amp;gt;500 million people worldwide. Despite insulin therapy, most patients develop devastating complications, emphasizing the need for curative strategies. Human multipotent stromal\/stem cells (MSC) secrete factors that promote islet regeneration. We previously showed that intrapancreatic (iPan) delivery of Wnt-activated MSC-conditioned media (Wnt+ CM) stimulates islet regeneration without cell transfer. This study aimed to identify and functionally validate specific MSC-secreted proteins with islet regenerative potential.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Comprehensive mass spectrometry-based, quantitative proteomic analyses comparing Wnt-pathway activated versus untreated MSC secretomes were cross-referenced with a prior dataset distinguishing regenerative from nonregenerative MSC CM. Proteins enriched in both conditions were iPan-injected individually or in combination into streptozotocin-treated NOD\/SCID mice. Nonfasting glucose, glucose tolerance, beta cell mass, islet morphology, and islet cell proliferation were assessed at 4- and 32-days post-treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Cross-referenced secretome analyses identified eight proteins implicated in islet regeneration: CALU, CTSB, FAM3C, GAL1, PPIA, PSAP, SOD1, and TGM2. A single iPan-injection of the 8-protein combination significantly lowered hyperglycemia, improved glucose tolerance, and increased beta cell mass, comparable to Wnt+ CM. Regenerative effects such as increased beta cell proliferation appeared as early as day 4. Single-protein testing identified CALU and SOD1 as leading candidates, improving glucose tolerance and reducing nonfasting glucose.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study defines a set of MSC-secreted proteins that promote islet regeneration in vivo, supporting the development of protein-based biologics to preserve or restore beta cell function during diabetes, with potential applications alongside islet replacement therapies to enhance graft survival and function.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/stcltm\/szag022","type":"journal-article","created":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T12:41:23Z","timestamp":1771936883000},"source":"Crossref","is-referenced-by-count":0,"title":["Discovery and validation of islet regenerative proteins secreted by human multipotent stromal cells"],"prefix":"10.1093","volume":"15","author":[{"given":"Xin Y","family":"Xie","sequence":"first","affiliation":[{"name":"Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University , London, ON N6A 5C1,","place":["Canada"]},{"name":"Molecular Medicine Research Laboratories, Robarts Research Institute , London, ON N6A 5B7,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nouran N","family":"Al-Banaa","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University , London, ON N6A 5C1,","place":["Canada"]},{"name":"Molecular Medicine Research Laboratories, Robarts Research Institute , London, ON N6A 5B7,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8992-844X","authenticated-orcid":false,"given":"Yina","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University , London, ON N6A 5C1,","place":["Canada"]},{"name":"Molecular Medicine Research Laboratories, Robarts Research Institute , London, ON N6A 5B7,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gillian I","family":"Bell","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University , London, ON N6A 5C1,","place":["Canada"]},{"name":"Molecular Medicine Research Laboratories, Robarts Research Institute , London, ON N6A 5B7,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miljan","family":"Kuljanin","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Western University , London, ON N6A 5C1,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tyler T","family":"Cooper","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Western University , London, ON N6A 5C1,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caleb J","family":"Podgers","sequence":"additional","affiliation":[{"name":"Molecular Medicine Research Laboratories, Robarts Research Institute , London, ON N6A 5B7,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ajaya","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University , London, ON N6A 5C1,","place":["Canada"]},{"name":"Molecular Medicine Research Laboratories, Robarts Research Institute , London, ON N6A 5B7,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anargyros","family":"Xenocostas","sequence":"additional","affiliation":[{"name":"Department of Haematology, London Health Sciences Centre , London, ON N6A 5W9,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gilles A","family":"Lajoie","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Western University , London, ON N6A 5C1,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2186-3166","authenticated-orcid":false,"given":"David A","family":"Hess","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University , London, ON N6A 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