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

非人类灵长类动物对复合胰岛肾移植的耐受性

• 批准号: 8432086
• 负责人: KAZUHIKO YAMADA
• 金额: $ 35万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8432086
• 关键词: Adverse effects; Allogenic; Animal Model; Cells; Child; Clinical Protocols; Data; Diabetic Nephropathy; End stage renal failure; Hematopoietic; Immunosuppression; Injection of therapeutic agent; Instruction; Insulin; Kidney; Kidney Failure; Kidney Transplantation; Living Donors; Macaca fascicularis; Macaca mulatta; Modality; Modeling; Morbidity - disease rate; Organ; Pancreas; Pancreas Transplantation; Pancreatectomy; Papio; Preparation; Procedures; Protocols documentation; Reporting; Research Proposals; Staging; Techniques; Translating; Transplantation; clinically relevant; design; diabetic; diabetic patient; islet; nonhuman primate; pre-clinical; type I diabetic

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

项目总结（见说明）： 尽管许多肾衰竭的糖尿病患者，特别是儿童，有潜在的捐赠者愿意提供肾脏和胰岛，但实现胰岛素非依赖性所需的胰岛数量阻碍了 通过活体供体的部分胰腺切除术成功地进行了胰岛移植。项目2旨在开发一种耐受诱导策略，用于使用活体供体复合胰岛-肾（IK）移植（Tx）治愈性治疗终末期糖尿病肾病。我们之前已经证明，在大型动物模型中移植预血管化胰岛作为IKs的一部分的策略是成功的，使用的胰岛比游离非血管化胰岛的Tx所需的胰岛少得多。肾功能和胰岛功能均得到恢复 通过IK Tx在肾切除的糖尿病狒狒中使用临床相关的免疫抑制方案跨越完全同种异体屏障。最近，我们的初步数据显示，在用造血细胞Tx治疗的恒河猴中，