Key Laboratory of Transplant Engineering and Immunology, Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, China.
Department of Endocrinology and Metabolism, Center for Diabetes and Metabolism Research, West China Hospital, Sichuan University, Chengdu, China.
J Cell Mol Med. 2022 Sep;26(18):4847-4858. doi: 10.1111/jcmm.17515. Epub 2022 Aug 17.
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.
移植到肝脏后，胰岛的显著功能障碍和丧失限制了该手术在临床上的广泛应用。活性氧和炎症等非免疫因素被认为是移植物衰竭的主要驱动力。脂肪因子脂联素在对抗炎症和氧化应激方面发挥着重要作用。先前的研究表明，全身性给予脂联素可显著防止移植后胰岛的损失并增强胰岛功能。体外研究表明，脂联素可保护胰岛免受缺氧/复氧损伤、氧化应激以及 TNF-α 诱导的损伤。通过应用腺病毒介导的转染，我们现在在胰岛移植前对胰岛细胞进行工程改造，使其表达外源性脂联素基因。腺病毒介导的脂联素转导到肾包膜下移植的同种异体亚最佳胰岛移植物中可显著预防炎症，保留胰岛移植物质量并改善胰岛移植结局。这些结果表明，腺病毒介导的脂联素基因治疗可能是胰岛移植中胰岛保存的一种有益的临床工程方法。
