NONHUMAN PRIMATE MODELS FOR HUMAN XENOTRANSPLANTATION

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。目的：使用非人类物种（异种移植）的器官，如猪，代表了目前可用于人体移植的器官严重短缺的解决方案。异种移植物会被抗体迅速排斥，这种抗体与猪细胞中存在的半乳糖碳水化合物结合，而在人类和旧大陆灵长类动物中不存在。将猪细胞置于含有猪肝细胞的生物人工肝脏后，暴露于猪细胞的人体内的异种抗体由IGHV3-11和IGHV3-74种系祖细胞编码。本研究的目的是：(1)鉴定恒河猴用于编码猪肝细胞和内皮细胞的异种抗体反应的免疫球蛋白VH基因；(2)确定恒河猴是否使用相同的Ig VH基因编码对分离肝细胞和来自猪供体的血管化肝移植物的异种抗体反应；(3)比较Ig VH基因编码对猪供体分离细胞（肝细胞和胰岛细胞）和血管化器官（心脏和肝脏）的异种抗体反应。

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.