Infectious Diseases and Clinical Xenotransplantation

Abstract

Xenotransplantation, transplantation into humans of vascularized organs or viable cells from nonhuman species, is a potential solution to shortages of transplantable human organs. Among challenges to application of clinical xenotransplantation are unknown risks of transmission of animal microbes to immunosuppressed recipients or the community. Experience in allotransplantation and in preclinical models suggests that viral infections are the greatest concern. Worldwide, the distribution of swine pathogens is heterogeneous and cannot be fully controlled by international agricultural regulations. It is possible to screen source animals for potential human pathogens before procuring organs in a manner not possible within the time available for surveillance testing in allotransplantation. Infection control measures require microbiological assays for surveillance of source animals and xenograft recipients and research into zoonotic potential of porcine organisms. Available data suggest that infectious risks of xenotransplantation are manageable and that clinical trials can advance with appropriate protocols for microbiological monitoring of source animals and recipients.

Keywords: Switzerland; United States; assay development; emerging infection; global warming; immunocompromised host; immunosuppression; infection control; infectious disease; viral infection; xenotransplantation; zoonoses.

Figure

Advances in genetic engineering have led to the breeding of pigs with advantages in infection, immunology, coagulation, size, and inflammation. Breeding of source animals in biosecure facilities enables screening for potential pathogens. B4GalNT2, glycosyltransferase; CD46, human membrane cofactor protein; CD47, block SIRPα tyrosine phosphorylation; CD55, human decay-accelerating factor; CMAH, cytidine monophosphate-N-acetylneuraminic acid hydroxylase; EPCR, endothelial cell protein C receptor; GGAT1, α-1,3-glycosyltransferase; HO1, heme oxygenase-1; HA20, human A20; PERV, porcine endogenous retrovirus; THBD, human thrombomodulin gene.