Size, availability and the physiologic, immunologic and anatomic similarities between swine and humans have made this species the most attractive potential donor for clinical xenotransplantation (XTx). However, until genetic modification of swine became possible, survivals of pig organs in primates were measured in days to weeks, despite the use of potent immunosuppressants and absorption of natural antibodies. Over the past 15 years, the use of knock-out and transgenic (Tg) swine donors has allowed marked increases in survival of xenograft organs, with heterotopic hearts surviving for over 2 years and life-supporting kidneys (XKTx) for greater than 6 months in baboon recipients. The results for other organs have lagged behind, although recent progress has also been reported for lungs (XLTx) and livers. It is clear that this remarkable progress has been due to genetic engineering of the donors. It is now important to address: (1) what additional genes should be altered; (2) where these gene(s) should be expressed; and (3) what negative effects may be caused by expression of human genes in porcine grafts. Data which provide some insight for answering these questions are now available from the recent experience of our own and other groups using GalT-KO pig donors expressing hCD47 with or without other transgenes in pig-to-baboon baboon XLTx and XKTx models.
