NONHUMAN PRIMATE MODELS FOR HUMAN XENOTRANSPLANTATION

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 使用专门培育的猪作为人体移植的器官捐赠者可能会给移植医学带来革命性的变化。目前有超过97000人在等待器官移植，但今年提供器官的捐赠者人数约为7000人。猪器官异种移植可以挽救生命，但这些移植物很快就会被与碳水化合物异种抗原(GAL碳水化合物)结合的抗体排斥。最近有报道称，半乳糖基转移酶基因敲除(GalTKO)猪的器官在移植到非人类灵长类动物体内后存活了3-6个月，这为成功培育GalTKO猪提供了新的乐观。然而，抗非半乳糖异种抗体沉积和血栓形成会阻碍移植物的长期存活。这项提议有两个主要目标。第一个是识别通过第二次基因改造来防止血栓形成的异种抗体，这些抗体启动了对GalTKO捐赠者的固体器官异种移植的排斥反应。第二个目标是对一种有前景的新型抗独特型抗体进行功能测试，该抗体可以识别体内诱导的异种反应性B细胞，以确定其在促进异种移植物存活方面的有效性。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The use of specifically bred pigs as organ donors for human transplantation could revolutionize transplantation medicine. There are over 97,000 people currently waiting for an organ transplant but the number of donors who provided organs this year was approximately 7000. Pig organ xenografts could save lives, but these grafts are rapidly rejected by antibodies that bind to a carbohydrate xenoantigen (gal carbohydrate). The successful development of galactosyltransferase knockout (GalTKO) pigs has provided renewed optimism after recent reports that GalTKO organs survive for 3-6 months after transplantation into non-human primates. Anti-non-gal xenoantibody deposition and thrombosis, however, prevent long-term graft survival. There are two major objectives of this proposal. The first is to identify the xenoantibodies that initiate rejection of solid organ xenografts from GalTKO donors with a second genetic modification to prevent thrombosis. The second objective is to functionally test a promising, novel anti-idiotypic antibody that identifies xenoreactive B cells induced in vivo for its efficacy in promoting survival of xenografts.