Therapeutic issues in the treatment of vascularized xenotransplants using gal-knockout donors in nonhuman primates

Solid organ xenotransplantation could be the future of transplantation, but improved outcomes are required in experimental models before clinical trials are justified. This review summarizes recent advances in solid organ xenotransplantation using organs from α1,3-galactosyltransferase gene-knockout (GTKO) pigs (with or without other genetic modifications) and novel therapeutic approaches.

Work on the development of genetically engineered pigs has been considerable during the past few years, with many research institutes reporting the outcomes of research. Multiple gene modifications on a GTKO background have been reported, and the results of transplantation using organs from these pigs have been published. Progress, however, has been variable, and several obstacles, for example, coagulation dysregulation, have been identified. Heterotopic pig heart xenotransplantation has been associated with graft survival up to 8 months, but kidney graft survival has not improved significantly.

The availability of GTKO pigs with additional genetic modifications aimed toward expression of multiple complement-regulatory proteins and/or human thromboregulatory genes, combined with novel immunosuppressive regimens, for example, the inclusion of B cell-depleting agents, should improve pig organ survival in the near future.