GENETICALLY-ENGINEERED PIG ORGAN TRANSPLANTATION IN BABOONS: IMMUNOLOGICAL AND FUNCTIONAL STUDIES CORE C: HISTOPATHOLOGY CORE. Histopathological evaluation of features of organ xenograft rejection (Core Lead: Jeremy Foote; Consultants: Henk-Jan Schuurman; Burcin Ekser, Sameer Al Diffalha; Huma Fatima; Silvio Litovsky) SUMMARY/ABSTRACT The transplantation (Tx) of kidneys and hearts from genetically-engineered pigs into nonhuman primates has recently been followed by increasing graft and recipient survival, extending to many months or even years. Pig liver Tx has been less successful, mainly through the development of an immediate thrombocytopenia (as the primate platelets are phagocytosed by cells in the liver graft). In the present study, GE pig kidney (Project 1), liver (Project 2), and heart (Project 3) grafts will be transplanted into immunosuppressed baboons and followed for 6 months (kidneys and hearts) or one month (livers). The pigs (Core A) will largely be of the same phenotype, and the immunosuppressive regimen will be almost identical in all 3 Projects. All of the immunological assays (Core B) and histopathological methods (Core C) will be standardized, enabling comparisons to be made in the results from all 3 Projects. Using state-of-the-art technology, Core C will therefore play an integral role in all three Projects, specifically in the identification of previously-characterized and novel pathways of transplant rejection or acceptance resulting from Tx of organs from multigene pigs, specifically those with 8 (8-gene) or more genetic manipulations. We will characterize known and novel histopathologic lesions to further our understanding of mechanisms of immune-mediated xenograft pathology and rejection, when present, to provide mechanistic insight that will be utilized to augment existing donor genetics and immune suppressive therapeutic regimens. The Core will use light microscopy, immunohistochemistry, and transmission electron microscopy to provide detailed data on each graft tissue examined. The Core Lead, Dr Foote, will be supported by other experts in experimental xenograft histopathology (Drs. Schuurman and Ekser), and by experts in clinical allograft histopathology (Drs. Fatima, Al Diffalha, and Litovsky).