Ischemic preconditioning increased the intestinal stem cell activities in the intestinal crypts in mice

Background: Ischemic preconditioning (IPC) can protect against ischemia-reperfusion injury in the small intestine. Because intestinal stem cells (ISCs) control the recovery and growth of intestinal villi, this study investigated whether IPC had any effects on the activity of ISCs. ;Materials and methods: The small intestines of mice were treated with IPC, laparotomy only (sham), or no surgery. The crypt fractions were isolated and the characteristics of ISCs among various groups were compared. The regenerative ability and the number of organoids grown from various crypt fractions were compared. The expression of hypoxiainducible factor-1 alpha (HIF-1 alpha) and the related proteins of the Wnt-/beta-catenin pathway in the crypt fractions were studied. ;Results: The IPC group had higher messenger RNA levels of various stem cell markers than the sham group at days 1 and 2 after surgery. The IPC group exhibited greater regenerative activity and more crypt organoids than the sham group (P < 0.05). The expression of HIF-1 alpha, beta-catenin, and phosphoglycogen synthase kinase 3 beta was increased in the IPC-treated crypt fractions in vivo and cultured crypt organoid cells with deferoxamine-mimicked hypoxia in vitro. ;Conclusions: IPC significantly upregulated the activity of ISCs, possibly through the HIF-1 alpha response and Wnt-/beta-catenin signaling pathway. (C) 2014 Elsevier Inc. All rights reserved