Xenotransplantation, or transplantation between individuals from different species, has long been investigated with the objective to solve the shortage of human organs, tissues and cells for clinical transplantation. Decades of research have convinced scientists that the pig is the most appropriate donor species. Indeed, in addition to numerous anatomical and physiological similarities between pig and man, pig husbandry lends itself to providing the large number of animals necessary to meet the clinical demand.
In the last few years, research in the field of solid organ xenotransplantation has made sensational progress. In particular, in vitro studies and pre-clinical research using pig-to-nonhuman primate transplantation models have clarified the key immunological and physiological barriers to xenotransplantation and provided a better comprehension of the mechanisms underlying the lesions observed in rejected xenografts. This has ultimately resulted in the genetic engineering of specifically-designed, more compatible donor pigs.
The present review article describes the major hurdles that need to be overcome to enable successful solid organ xenotransplantation in humans. These include immunological, physiological and biosafety issues. Discussion on the ideal organ source and on the selection of the most appropriate candidates for first-in-human studies is provided. Particular attention has been dedicated to kidney xenotransplantation. Indeed, at this stage it would appear that the critical immunological and physiological obstacles to clinical xenotransplantation have never been perceived as surmountable as they appear today.
Keywords: Kidney, Patient selection, Genetically-engineered pigs, Xenotransplantation, Physiology