DEVELOPMENT OF RODENT MODELS FOR XENOTRANSPLANTATION

该研究项目旨在开发相关的，具有成本效益的 用于人类异种移植的啮齿动物模型。 《公约》概述的工作 本发明的目的是：（1）交换心脏异种移植物， 选定的供体/受体物种组合组，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亚群，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 单门/受体物种组合中异种移植物，和（4）使用大鼠 用于分离和表征异种移植靶的单克隆抗体 抗原，首先在仓鼠，后来在相关物种，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中进行的实验， 人类 从这些研究中获得的信息对以下方面很重要： 定义哪些种类的小动物可以被认为是代表 人猪和/或灵长类异种移植的最佳模型。 的定义 用于人类异种移植的最合适的啮齿动物模型具有 研究人员在许多医学研究领域广泛使用的潜力， 特别是那些使用来自非人供体的组织的方法 作为糖尿病等疾病的新治疗策略的一部分， 神经系统疾病、心血管疾病和特定基因 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.