TRANSLATIONAL STRATEGIES FOR PANCREATIC ISLET XENOTRANSPLANTATION IN NHP

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 在过去的一年里，我们解决了上一次报告期间所经历的成功减少的问题。在解决了新生猪胰岛的分离和加工，以及一种新的链佐菌素诱导非人类灵长类糖尿病的方法后，我们成功地将猪胰岛移植到糖尿病受体猕猴体内，并在共刺激阻断免疫抑制方案的覆盖下，持续缓解了高血糖，并使猪胰岛存活了180天。在我们的异种胰岛非人类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被应用到我们的异种胰岛模型中，取得了非常有希望的结果。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位置，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.