Xenotransplantation-Progress and Problems: A Review

Abstract

Xenotransplantation using pig cells, tissues or organs is considered to be a solution to the shortage of human allotransplants. Pigs have been selected as optimal donor for several reasons, among them physiological and economical. Before xenotransplantation will be applied broadly in the clinic three hurdles need to be overcome: (i) rejection due to immune reactions and coagulation dysfunction, (ii) physiological incompatibility and (iii) microbiological risk. Although some clinical trials have been performed in the past and some are ongoing, most experience is gained from pig-to-non human primate experiments. To overcome immune rejection, numerous multitransgenic and knock-down animals were produced or are in preparation. The physiological compatibility is still badly studied, mainly due to the short survival time of the recipient animals. Last not least, xenotransplantation may be associated with the risk of transmission of porcine microorganisms. Most of them can be eliminated by designated pathogen free breeding of the animals; however, porcine endogenous retroviruses (PERVs) represent a special risk. PERVs are integrated as proviruses in the genome of all pigs, they can be released as viral particles and infect human cells. An extensive screening program and selection of donor animals with a low expression of PERV accompanied by the development of different strategies to prevent PERV transmission is therefore requested. Finally, a broad discussion within the scientific community and the society concerning ethical aspects of xenotransplantation had been taken place.