Significant pancreatic islet dysfunction and loss shortly after transplantation to the liver limit the widespread implementation of this procedure in the clinic. Nonimmune factors such as reactive oxygen species and inflammation have been considered as the primary driving force for graft failure. The adipokine adiponectin plays potent roles against inflammation and oxidative stress. Previous studies have demonstrated that systemic administration of adiponectin significantly prevented islet loss and enhanced islet function at post-transplantation period. In vitro studies indicate that adiponectin protects islets from hypoxia/reoxygenation injury, oxidative stress as well as TNF-α-induced injury. By applying adenovirus mediated transfection, we now engineered islet cells to express exogenous adiponectin gene prior to islet transplantation. Adenovirus-mediated adiponectin transfer to a syngeneic suboptimal islet graft transplanted under kidney capsule markedly prevented inflammation, preserved islet graft mass and improved islet transplant outcomes. These results suggest that adenovirus-mediated adiponectin gene therapy would be a beneficial clinical engineering approach for islet preservation in islet transplantation.
Bibliographical noteFunding Information:
This study was supported by the Program of National Natural Science Foundation of China (81801589, 82070846), China Postdoctoral Science Foundation (2018 M643487), 1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University (ZYGD18014, ZYGD18017), Center of Excellence‐International Collaboration Initiative Grant of West China Hospital (139180012) and Program for Overseas High‐Level Talents Introduction of Sichuan Province of China (21RCYJ0046).
Program of National Natural Science Foundation of China: 81801589, 82070846. China Postdoctoral Science Foundation: 2018M643487. 1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University: ZYGD18014, ZYGD18017. Center of Excellence‐International Collaboration Initiative Grant of West China Hospital: 139180012. Program for Overseas High‐Level Talents Introduction of Sichuan Province of China: 21RCYJ0046.
© 2022 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.
- gene therapy
- hypoxia/reoxygenation injury
- islet transplantation
- oxidative stress