NONHUMAN PRIMATE MODELS FOR HUMAN XENOTRANSPLANTATION

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来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 使用专门培育的猪作为人体移植的器官供体可能会给移植医学带来革命性的变化。目前有超过97，000人等待器官移植，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（半乳糖碳水化合物）结合的抗体排斥。半乳糖基转移酶敲除（GalTKO）猪的成功开发为最近的报告提供了新的乐观情绪，该报告称GalTKO器官在移植到非人灵长类动物后存活3 - 6个月。然而，抗非半乳糖异种抗体沉积和血栓形成阻止了移植物的长期存活。这项建议有两个主要目标。第一个是鉴定引发来自GalTKO供体的实体器官异种移植物排斥的异种抗体，所述供体具有第二遗传修饰以防止血栓形成。 第二个目的是功能测试一种有前途的新型抗独特型抗体，该抗体鉴定体内诱导的异种反应性B细胞，以确定其促进异种移植物存活的功效。

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. 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.