This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The use of specifically bred pigs as organ donors for human transplantation could revolutionize transplantation medicine. There are over 97,000 people currently waiting for an organ transplant but the number of donors who provided organs this year was approximately 7000. Pig organ xenografts could save lives, but these grafts are rapidly rejected by antibodies that bind to a carbohydrate xenoantigen (gal carbohydrate). The successful development of galactosyltransferase knockout (GalTKO) pigs has provided renewed optimism after recent reports that GalTKO organs survive for 3-6 months after transplantation into non-human primates. Anti-non-gal xenoantibody deposition and thrombosis, however, prevent long-term graft survival. There are two major objectives of this proposal. The first is to identify the xenoantibodies that initiate rejection of solid organ xenografts from GalTKO donors with a second genetic modification to prevent thrombosis. The second objective is to functionally test a promising, novel anti-idiotypic antibody that identifies xenoreactive B cells induced in vivo for its efficacy in promoting survival of xenografts.
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