Xenotransplantation tolerance: applications for recent advances in modified swine.

Abstract

The aim of this study was to review the recent progress in xenotransplantation achieved through genetic engineering and discuss the potential of tolerance induction to overcome remaining barriers to extended xenograft survival. The success of life-saving allotransplantation has created a demand for organ transplantation that cannot be met by the supply of human organs. Xenotransplantation is one possible solution that would allow for a nearly unlimited supply of organs. Recent genetic engineering of swine has decreased the reactivity of preformed antibodies to some, but not all, potential human recipients. Experiments using genetically modified swine organs have now resulted in survival of life-supporting kidneys for over a year. However, the grafts show evidence of antibody-mediated rejection on histology, suggesting additional measures will be required for further extension of graft survival. Tolerance induction through mixed chimerism or thymic transplantation across xenogeneic barriers would be well suited for patients with a positive crossmatch to genetically modified swine or relatively negative crossmatches to genetically modified swine, respectively. This review highlights the current understanding of the immunologic processes in xenotransplantation and describes the development and application of strategies designed to overcome them from the genetic modification of the source animal to the induction of tolerance to xenografts.