NONHUMAN PRIMATE MODELS FOR HUMAN XENOTRANSPLANTATION

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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.