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

Solid organ xenotransplantation could be the future oftransplantation, but improved outcomes are required in experimental models beforeclinical trials are justified. This review summarizes recent advances in solidorgan xenotransplantation using organs from α1,3-galactosyltransferasegene-knockout (GTKO) pigs (with or without other genetic modifications) and noveltherapeutic approaches.RECENT FINDINGS: Work on the development of genetically engineered pigs has been considerable during the past few years, with many research institutes reportingthe outcomes of research. Multiple gene modifications on a GTKO background havebeen reported, and the results of transplantation using organs from these pigshave been published. Progress, however, has been variable, and several obstacles,for example, coagulation dysregulation, have been identified. Heterotopic pigheart xenotransplantation has been associated with graft survival up to 8 months,but kidney graft survival has not improved significantly.SUMMARY: The availability of GTKO pigs with additional genetic modificationsaimed toward expression of multiple complement-regulatory proteins and/or humanthromboregulatory genes, combined with novel immunosuppressive regimens, forexample, the inclusion of B cell-depleting agents, should improve pig organsurvival in the near future.