Adiponectin gene therapy prevents islet loss after transplantation. Issue 18 (17th August 2022)

• Record Type: Journal Article
• Authors: Wang, Chengshi; Du, Xiaojiong; Fu, Fudong; Li, Xiaoyu; Wang, Zhenghao; Zhou, Ye; Gou, Liping; Li, Wei; Li, Juan; Zhang, Jiayi; Liao, Guangneng; Li, Lan; Han, Yuan‐Ping; Tong, Nanwei; Liu, Jingping; Chen, Younan; Cheng, Jingqiu; Cao, Qi; Ilegems, Erwin; Lu, Yanrong; Zheng, Xiaofeng; Berggren, Per‐Olof
• Is Part Of: Journal of cellular and molecular medicine. Volume 26:Issue 18(2022)
• Page Start: 4847
• Page End: 4858
• Publication Date: 2022-08-17
• Subjects: Adiponectin -- gene therapy -- hypoxia/reoxygenation injury -- inflammation -- islet transplantation -- oxidative stress; Cytology; Medicine; Molecular Biology; Cytologie -- Périodiques; Médecine -- Périodiques; Biologie moléculaire -- Périodiques; Cytology -- Periodicals; Medicine -- Periodicals; Molecular biology -- Periodicals; 611.01805
• DOI: 10.1111/jcmm.17515
• Languages: English
• ISSNs: 1582-1838

Abstract

Abstract: 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.