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。子项目及 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。 目的：使用来自非人类物种（异种移植物）如猪的器官代表了目前可用于人类移植的器官严重短缺的解决方案。异种移植物被抗体迅速排斥，抗体与猪细胞上存在而人类和旧世界灵长类动物中不存在的半乳糖碳水化合物结合。 在置于含有猪肝细胞的生物人工肝上后暴露于猪细胞的人中的异种抗体由IGHV 3 -11和IGHV 3 -74生殖系祖细胞编码。本研究的目的是（1）鉴定恒河猴用于编码针对单个猪肝细胞和内皮细胞的异种抗体应答的免疫球蛋白VH基因;（2）确定恒河猴是否使用相同的IG VH基因来编码针对来自猪供体的分离肝细胞和血管化肝移植物的异种抗体应答;（3）比较编码对来自猪供体的分离细胞（肝细胞和胰岛细胞）和血管化器官（心脏和肝脏）的异种抗体应答的IG VH基因。

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. Objective: The use of organs from nonhuman species (xenografts) such as pigs represents a solution for the acute shortage of organs currently available for human transplantation. Xenografts are rapidly rejected by antibodies that bind to the gal carbohydrate that is present on pig cells and absent in humans and Old World primates. Xenoantibodies in humans exposed to pig cells following placement on a bioartificial liver containing pig hepatocytes are encoded by the IGHV3-11 and IGHV3-74 germline progenitors. The objectives of this study were to (1) identify the immunoglobulin VH genes used by rhesus monkeys to encode xenoantibody responses to individual porcine hepatocytes and endothelial cells; (2) determine whether rhesus monkeys use the same Ig VH genes to encode xenoantibody responses to both isolated hepatocytes and vascularized liver grafts from porcine donors; (3) compare the Ig VH genes that encode xenoantibody responses to both isolated cells (hepatocytes and pancreatic islet cells) and vascularized organs (heart and liver) from porcine donors.