Gene combination transfer to block autoimmune damage in transplanted islets of Langerhans.

Suzanne Bertera, Angela M Alexander, Megan L Crawford, Glenn Papworth, Simon C Watkins, Paul D Robbins, Massimo Trucco
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引用次数: 23

Abstract

Islet transplantation therapy would be applicable to a wider range of diabetic patients if donor islet acceptance and protection were possible without systemic immunosuppression of the recipient. To this aim, gene transfer to isolated donor islets ex vivo is one method that has shown promise. This study examines the combined effect of selected immunomodulatory and anti-inflammatory genes known to extend the functional viability of pancreatic islet grafts in an autoimmune system. These genes, indoleamine 2,3-dioxygenase (IDO), manganese superoxide dismutase (MnSOD), and interleukin (IL)-1 receptor antagonist protein (IRAP), were transferred to isolated NOD donor islets ex vivo then transplanted to NODscid recipients and evaluated in vivo after diabetogenic T-cell challenge. The length of time the recipient remained euglycemic was used to measure the ability of the transgenes to protect the graft from autoimmune destruction. Although the results of these cotransfections gave little evidence of a synergistic relationship, they were useful to show that gene combinations can be used to more efficiently protect islet grafts from diabetogenic T cells.

基因联合转移阻断朗格汉斯移植胰岛自身免疫损伤
如果供体胰岛的接受和保护不需要对受体进行全身免疫抑制,胰岛移植治疗将适用于更广泛的糖尿病患者。为此目的,基因转移到离体供体胰岛是一种有希望的方法。本研究考察了已知的免疫调节和抗炎基因的联合作用,这些基因可以延长胰岛移植物在自身免疫系统中的功能活力。这些基因,吲哚胺2,3-双加氧酶(IDO),锰超氧化物歧化酶(MnSOD)和白细胞介素(IL)-1受体拮抗剂蛋白(IRAP),被转移到离体NOD供体胰岛,然后移植到NODscid受体,并在糖尿病t细胞攻击后进行体内评估。受体保持血糖正常的时间长度用于测量转基因保护移植物免受自身免疫破坏的能力。虽然这些共转染的结果几乎没有提供协同关系的证据,但它们有助于表明基因组合可用于更有效地保护胰岛移植物免受糖尿病性T细胞的侵害。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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