Pig-to-nonhuman primate organ xenotransplantation

Abstract

Purpose of review The availability of α1,3-galactosyltransferase gene-knockout pigs in which the major target for primate anti-pig antibodies has been deleted is considered a major step toward clinical xenotransplantation. A review of progress in pig-to-nonhuman primate transplantation is therefore timely. Recent findings Several groups have continued their studies using pigs transgenic for one or more human complement regulatory proteins, with graft survival reaching more than 3 months in some cases. Significant complications have resulted from the intensity of immunosuppression required to achieve these results, however. The use of organs from α1,3-galactosyltransferase gene-knockout pigs has eliminated hyperacute rejection in baboons. Heterotopic heart α1,3-galactosyltransferase gene-knockout xenografts maintained with chronic immunosuppression survived up to 6 months, with graft failure associated with thrombotic microangiopathy. Life-supporting renal xenografts maintained with a tolerance-inducing regimen survived over 80 days, with the longest survivors dying with functioning grafts. Summary The availability of α1,3-galactosyltransferase gene-knockout donor pigs has eliminated the need for inhibition of antibodies to α1,3 galactose (Gal) or complement to prevent hyperacute rejection. It has also had a positive impact on the survival of heterotopic xenogeneic hearts transplanted under chronic immunosuppression and on the survival of orthotopic kidneys transplanted with donor thymus tissue in an attempt to induce tolerance. Problems remain to be resolved, including the effects of the variable presence of antibodies to non-Gal antigens, the high incidence of thrombotic microangiopathy in heart xenotransplants, and loss of animals to other causes in the recipients of orthotopic renal transplants. Nevertheless, the results with α1,3-galactosyltransferase gene-knockout donors are encouraging for the future of this field.