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Mechanistically, we found that the regenerated exocrine pancreas elevated interleukin-6 (IL-6) in PMSC implants, which transiently activated tumor necrosis factor\u2013\u03b1 (TNF-\u03b1) and interferon-\u03b3 (IFN-\u03b3) to inhibit IL-17, thereby rescuing damaged exocrine pancreas and islet \u03b2 cells. In addition, we used knockout mouse models to show that global lack of IL-6, TNF-\u03b1, or IFN-\u03b3 resulted in increased severity of STZ-induced diabetes and resistance to PMSC implantation therapy, confirming the roles of these factors in safeguarding pancreatic \u03b2 cells. Furthermore, removal of the kidney capsule PMSC implants at 28 days after implantation did not affect the PMSC-initiated therapeutic effect on diabetic mice. This study reveals a previously unknown role of exocrine pancreas regeneration in safeguarding \u03b2 cells and demonstrates a \u201csoil-rescues-seed\u201d strategy for type 1 diabetes therapy.<\/jats:p>","DOI":"10.1126\/scitranslmed.abg9170","type":"journal-article","created":{"date-parts":[[2022,8,3]],"date-time":"2022-08-03T17:56:13Z","timestamp":1659549373000},"source":"Crossref","is-referenced-by-count":21,"title":["Exocrine pancreas regeneration modifies original pancreas to alleviate diabetes in mouse models"],"prefix":"10.1126","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9680-0077","authenticated-orcid":true,"given":"Xiaoxing","family":"Kou","sequence":"first","affiliation":[{"name":"Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, South China Center of Craniofacial Stem Cell Research, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou 510055, China."},{"name":"Department of Anatomy and Cell Biology, University of Pennsylvania, School of Dental Medicine, Philadelphia, PA 19104, USA."},{"name":"Key Laboratory of Stem Cells and Tissue Engineering (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, University of Pennsylvania, School of Dental Medicine, Philadelphia, PA 19104, USA."},{"name":"Laboratory for Aging Research, State Key Laboratory of Biotherapy and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu 610041, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dandan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Yu","sequence":"additional","affiliation":[{"name":"Division of Transplantation, Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Can","family":"Li","sequence":"additional","affiliation":[{"name":"Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, South China Center of Craniofacial Stem Cell Research, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou 510055, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3356-8810","authenticated-orcid":true,"given":"Lu","family":"Lu","sequence":"additional","affiliation":[{"name":"Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, South China Center of Craniofacial Stem Cell Research, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou 510055, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2899-1208","authenticated-orcid":true,"given":"Chider","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, University of Pennsylvania, School of Dental Medicine, Philadelphia, PA 19104, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dawei","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, University of Pennsylvania, School of Dental Medicine, Philadelphia, PA 19104, USA."},{"name":"Department of Orthodontics, Peking University School &amp; 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