Strategies to Combat Hypoxia in Encapsulated Islet Transplan | 40543


国际标准期刊号 - 2161-1076


Strategies to Combat Hypoxia in Encapsulated Islet Transplantation

Rahul Krishnan ,David Ko ,Tori Tucker ,Emmanuel Opara ,Clarence E Foster III ,David Imagawa ,Michael Stamos ,Jonathan RT Lakey *

Islet transplantation has been shown as a possible treatment for Type 1 Diabetes. However, immediately following transplantation, islets face acute hypoxic stress due to the lack of vascularization of the newly transplanted tissue. It has been observed that up to 60% of newly transplanted islets perish during the first 48 hours post-transplantation as a direct result of hypoxic injury. This period of hypoxia needs to be reduced to maintain transplanted islet efficacy. Optimal function of immunoisolated islets requires adequate supply of oxygen to metabolically active insulin producing β-cells. An improved understanding of the interplay between oxygen diffusion and consumption rate in devices is critical for the design of means to improve oxygen supply to islets. Post-transplant graft failure and islet death have been postulated to result from hypoxia encountered immediately after transplantation, due to poor implant-site vascularization. In order to survive and function adequately, transplanted islets must be able to withstand the transient hypoxic shock until they are adequately vascularized. This review will explore the various mechanisms that result in loss of cell viability and insulin release from islets when they are exposed to hypoxic conditions, and summarize the various strategies that are being employed by researchers across the world to address this important issue to enable rapid translation of results obtained in pre-clinical trials to primate and human trials.