Clinical islet transplantation has relied almost exclusively on intraportal administration of pancreatic islets, as it has been the only consistent approach to achieve robust graft function in human recipients. However, this approach suffers from significant loss of islet mass from a potent immediate blood-mediated inflammatory response (IBMIR) and a hypoxic environment. To avoid these negative aspects of the portal site, we explored an alternative approach in which allogeneic islets were transplanted into the intrapleural space of a non-human primate (NHP), treated with an immunosuppression regimen previously reported to secure routine survival and tolerance to allogeneic islets in NHP. Robust glycemic control and graft survival were achieved for the planned study period of >90 days. Our observations suggest the intrapleural space provides an attractive locale for islet transplantation due to its higher oxygen tension, ability to accommodate large transplant tissue volumes, and a lack of IBMIR-mediated islet damage. Our preliminary results reveal the promise of the intrapleural space as an alternative site for clinical islet transplantation in the treatment of type 1 diabetes.

中文翻译：

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同种异体胰岛的胸腔内移植实现了糖尿病非人灵长类动物的血糖控制

临床胰岛移植几乎完全依赖胰岛的门静脉内给药，因为它是在人类受体中实现强大移植功能的唯一一致方法。然而，这种方法会因强烈的即时血液介导的炎症反应 (IBMIR) 和缺氧环境而导致胰岛质量显着下降。为了避免门户站点的这些负面影响，我们探索了一种替代方法，其中将同种异体胰岛移植到非人类灵长类动物 (NHP) 的胸膜腔内，用先前报道的免疫抑制方案治疗以确保常规存活和对同种异体细胞的耐受性NHP 中的胰岛。在 >90 天的计划研究期间实现了稳健的血糖控制和移植物存活。我们的观察表明，由于其较高的氧张力、容纳大量移植组织体积的能力以及缺乏 IBMIR 介导的胰岛损伤，胸膜内空间为胰岛移植提供了一个有吸引力的场所。我们的初步结果揭示了胸膜腔作为临床胰岛移植治疗 1 型糖尿病的替代部位的前景。