Analysis of potential porcine endogenous retrovirus (PERV) transmission ina whole-organ xenotransplantation model without interfering microchimerism

The question whether porcine xenografts can lead to porcine endogenous retr ovirus (PERV) infection of recipients is critical for the evaluation of the safety of pig-to-man xenotransplantation. Unfortunately, polymerase chain reaction (PCR)-based analysis of potential PERV infections in nonhuman-prim ate whole-organ xenotransplantation models is hampered by false positive re sults due to chimeric porcine cells. To avoid the inherent analytical probl em of xenomicrochimerism, we developed a non-life-supporting pig-to-primate kidney xenotransplantation model: porcine kidneys were transplanted, where as the functioning recipient kidneys remained in situ. Subsequent to reject ion (after 2 hours to 15 days), xenografts were removed, and recipients rem ained alive for up to 287 days. Immunosuppressive therapy based on cyclopho sphamide, cyclosporine, and steroids was maintained for 28 days after trans plantation. Using appropriate PCR assays, xenochimerism was found in tissue samples and partly even in peripheral blood leukocytes (PBLs) while the po rcine kidneys were in situ. After graft removal, xenochimerism was no longe r detectable, thus allowing analysis for possible PERV transmission.