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Amniotic fluid stem cells (AFSC) are beneficial in experimental intestinal diseases. Tumor necrosis factor\u2010induced protein 6 (TSG\u20106) has been shown to exert anti\u2010inflammatory effects. We aimed to investigate if AFSC secreted TSG\u20106 reduces inflammation and rescues intestinal I\/R injury. The superior mesenteric artery of 3\u2010week\u2010old rats was occluded for 90\u00a0minutes and green fluorescent protein\u2010labeled AFSC or recombinant TSG\u20106 was injected intravenously upon reperfusion. AFSC distribution was evaluated at 24, 48, and 72\u00a0hours after I\/R. AFSC and TSG\u20106 effects on the intestine were assessed 48\u00a0hours postsurgery. Intestinal organoids were used to study the effects of TSG\u20106 after hypoxia\u2010induced epithelial damage. After I\/R\u2010induced intestinal injury, AFSC migrated preferentially to the ileum, the primary site of injury, through blood circulation. Engrafted AFSC reduced ileum injury, inflammation, and oxidative stress. These AFSC\u2010mediated beneficial effects were dependent on secretion of TSG\u20106. Administration of TSG\u20106 protected against hypoxia\u2010induced epithelial damage in intestinal organoids. Finally, TSG\u20106 attenuated intestinal damage during I\/R by suppressing genes involved in wound and injury pathways. This study indicates that AFSC or TSG\u20106 have the potential of rescuing the intestine from the damage caused by I\/R.<\/jats:p>","DOI":"10.1096\/fj.201902892rr","type":"journal-article","created":{"date-parts":[[2020,3,29]],"date-time":"2020-03-29T04:49:07Z","timestamp":1585457347000},"page":"6824-6836","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["The intestinal injury caused by ischemia\u2010reperfusion is attenuated by amniotic fluid stem cells via the release of tumor necrosis factor\u2010stimulated gene 6 protein"],"prefix":"10.1096","volume":"34","author":[{"given":"Yuhki","family":"Koike","sequence":"first","affiliation":[{"name":"Division of General and Thoracic Surgery Translational Medicine The Hospital for Sick Children Toronto ON Canada"},{"name":"Department of Gastrointestinal and Paediatric Surgery Mie University Graduate School of Medicine Tsu 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