Pigs as xenogeneic donors

The success and widespread acceptance of clinical allotransplantation has led to a shortage of cadaveric organs and a resurgence of interest in xenotransplantation. Although swine are generally regarded as the preferred source of xenogeneic organs, the severe immunologic response to swine organs has so far precluded their clinical use. However, the past 10 years have seen many advances in the field, especially the use of genetically modified swine. These include animals transgenic for human complement regulatory proteins, and most recently, animals not expressing the alpha 1,3-galactosyltransferase gene (GalT-KO swine), produced by nuclear transfer. The initial results using GalT-KO swine as donors to nonhuman primates demonstrated survival of a life-supporting renal graft for up to 83 days without rejection when combined with a regimen designed to induce tolerance by vascularized donor thymic grafts. Although the initial results are encouraging, further improvements will be needed to warrant a clinical trial of xenotransplantation. In this review, we discuss immunologic barriers to xenotransplantation and recent attempts to overcome them, strategies to induce tolerance across a xenogenic barrier, and issues that will need to be considered before a clinical trial is attempted.