Tolerance to Composite Islet-Kidney Transplants in Non-Human Primates

项目总结(见说明)： 尽管许多有肾功能衰竭的糖尿病患者，特别是儿童，有潜在的捐赠者愿意同时提供肾脏和胰岛，但实现胰岛素独立所需的胰岛数量受阻。 活体供体胰腺部分切除成功移植胰岛。项目2旨在开发一种耐受性诱导策略，用于使用活体供体复合胰岛-肾移植(TX)治疗终末期糖尿病肾病。我们先前已经证明，在大型动物模型中移植预血运胰岛作为IKS的一部分是成功的，使用的胰岛比移植自由的、非血运胰岛所需的胰岛要少得多。肾和胰岛功能均已恢复。 通过使用临床相关的免疫抑制方案，在肾脏切除的糖尿病狒狒中，通过IK TX跨越完全同种异体屏障。最近，我们的初步数据显示，用造血细胞TX治疗恒河猴成功地诱导了iKs的耐受。

PROJECT SUMMARY (See instructions): Although many diabetic patients in renal failure, especially children, have potential donors willing to provide both a kidney and islets, the quantity of islets necessary to achieve insulin independence hampers successful islet Tx by partial pancreatectomy from living donors. Project 2 is designed toward developing a tolerance-inducing strategy for curative treatment of end-stage diabetic nephropathy using living donor composite Islet-Kidney (IK) transplantation (Tx). We have previously demonstrated that the strategy of transplanting pre-vascularized islets as part of IKs in large animal models is successful, using far fewer islets than are required for Tx of free, non-vascularized islets. Both renal and islet function were restored by IK Tx across fully allogeneic barriers in nephrectomized diabetic baboons using a clinically relevant immunosuppression protocol. More recently, our preliminary data have shown the successful induction of tolerance of IKs in rhesus monkeys treated with hematopoietic cell Tx in a