TRANSLATIONAL STRATEGIES FOR PANCREATIC ISLET XENOTRANSPLANTATION IN NHP

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 研究中心，而研究中心不一定是研究者所在的机构。 在过去一年中，我们解决了上一个报告所述期间成功率下降的问题。在解决了涉及新生猪胰岛的分离和处理以及链脲佐菌素诱导非人灵长类动物糖尿病的新方法等一系列技术问题后，我们已经能够重现将猪胰岛移植到受体糖尿病猕猴体内的最初成功，并在基于共刺激阻断的免疫抑制方案的掩护下，持续解决高血糖症和猪胰岛存活180天。在我们的同种异体胰岛非人灵长类动物模型的成功指导下，更有利的和临床相关的治疗方案应用于我们的异种胰岛模型，结果非常有希望。一旦优化，新的药物方案将用于确定最佳的胰岛质量和植入部位，为猪胰岛移植进入临床试验奠定基础。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. During the past year, we solved the problem of reduced success experienced during the previous report period. After resolving a number of technical problems involving the isolation and processing of the neonatal porcine islets, and a new nonhuman primate diabetes induction method by streptozocin, we have been able to reproduce our original success of transplanting porcine islets into recipient diabetic macaques with sustained resolution of hyperglycemia and survival of porcine islets for 180 days under cover of a costimulation blockade-based immunosuppression regimen. Guided by success in our alloislet nonhuman primate model, more favorable and clinically relevant treatment protocols were applied to our xenoislet model with very promising results. Once optimized, the new drug regimen will be used to determine the optimal islet mass and implantation site, establishing a foundation for moving porcine islet transplantation into clinical trials.