DEVELOPMENT OF RODENT MODELS FOR XENOTRANSPLANTATION

这项研究项目旨在开发相关的、成本效益高的 用于人类异种移植的啮齿动物模型。中概述的工作 本提案旨在：(1)交换异种心脏移植物 选定的捐赠者/受赠者物种组合群体，并建立 异种移植反应类型的免疫病理学特征 观察；(2)确定免疫球蛋白基因和B细胞的性质 控制对异种移植物的体液反应的子集以及这是否 不同供体物种的反应是一致的；(3)比较 心脏、肝脏、肾脏和胰岛的排斥反应模式 单个门/受体物种组合中的异种移植，以及(4)使用大鼠 用于分离和鉴定异种移植靶点的单抗 抗原，首先在仓鼠中，后来在相关物种中，以建立 最合适的物种组合，为类似的 在可能作为潜在异种移植供体的物种上进行实验 人类。从这些研究中获得的信息将对 定义哪些种类的小动物可以被认为代表 人、猪和/或灵长类动物异种移植的最佳模型。概念的定义 最适合用于人类异种移植的啮齿动物模型是 研究人员在医学研究的许多领域中广泛使用的潜力， 尤其是那些使用来自非人类捐赠者的组织的情况 作为糖尿病等疾病新治疗策略的一部分， 神经功能障碍、心血管疾病与特定基因 治疗。

This research project is designed to develop relevant, cost effective rodent models for human xenotransplantation. The work outlined in the present proposal is designed to: (1) exchange cardiac xenografts between selected groups of donor/recipient species combinations and establish the immunopathologic characteristics of the type of xenograft reaction observed; (2) establish the nature of the immunoglobulin genes and B cell subsets that control the humoral response to xenografts and whether this response is consistent for different donor species; (3) compare the pattern of rejection for cardiac, liver, kidney, and pancreatic islet xenografts in a single door/recipient species combination, and (4) use rat monoclonal antibodies to isolate and characterize xenograft target antigens, first in hamster and later in related species, to establish the most appropriate species combination for providing the basis for similar experiments in species that may serve as potential xenograft donors for humans. The information derived from these studies will be important for defining which species of small animals can be considered to represent the best models for human pig and/or primate xenografting. The definition of the most appropriate rodent model for human xenotransplantation has the potential for wide use by investigators in many areas of medical research, especially those in which the use of tissues from non-human donors are used as a part of new treatment strategies for diseases such as diabetes, neurological disorders, cardiovascular disease and specific gene therapies.