The intestinal injury caused by ischemia‐reperfusion is attenuated by amniotic fluid stem cells via the release of tumor necrosis factor‐stimulated gene 6 protein

Ischemia/reperfusion (I/R) is implicated in the pathogenesis of various acute intestinal injuries. Amniotic fluid stem cells (AFSC) are beneficial in experimental intestinal diseases. Tumor necrosis factor‐induced protein 6 (TSG‐6) has been shown to exert anti‐inflammatory effects. We aimed to investigate if AFSC secreted TSG‐6 reduces inflammation and rescues intestinal I/R injury. The superior mesenteric artery of 3‐week‐old rats was occluded for 90 minutes and green fluorescent protein‐labeled AFSC or recombinant TSG‐6 was injected intravenously upon reperfusion. AFSC distribution was evaluated at 24, 48, and 72 hours after I/R. AFSC and TSG‐6 effects on the intestine were assessed 48 hours postsurgery. Intestinal organoids were used to study the effects of TSG‐6 after hypoxia‐induced epithelial damage. After I/R‐induced 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‐mediated beneficial effects were dependent on secretion of TSG‐6. Administration of TSG‐6 protected against hypoxia‐induced epithelial damage in intestinal organoids. Finally, TSG‐6 attenuated intestinal damage during I/R by suppressing genes involved in wound and injury pathways. This study indicates that AFSC or TSG‐6 have the potential of rescuing the intestine from the damage caused by I/R.