Early islet graft failure due to hypoxia: review and our experimental experience

Pancreas and islet transplantation is the only treatment that can cure type 1 diabetes mellitus. Less invasive and more targeted surgical and immunosuppressive regimens make islet transplantation a more attractive treatment for type 1 diabetes. Current methods of islet isolation and purification cause hypoxic stress to which β cells are extremely vulnerable. Transplanted islets need to re-establish their vascular system in order to obtain sufficient oxygen and nutrient supply for stable engraftment. However, this process takes at least 7- 14 days to complete. Massive (＞50%) β cells are dead before revascularization due to hypoxia, especially the core of the islets. Therefore, the obvious critical problem is the circulatory deficit to which the islets are susceptible in the immediate post-transplant period.In the current study, we reviewed various hypoxic-related insults to islets before complete engraftment, and feasible strategies to reduce hypoxic-induced apoptosis based on our experimental experiences together with that of others and investigated the possibility of revascularization in islet transplantation. Key words: Islet transplantation; Hypoxia; HIF1α; Revascularization; Oxidative stress