Early testing of porcine organ xenotransplantation products in humans: Microbial safety as illustrated for porcine cytomegalovirus.

Abstract

Sincemid-2021, a number of exploratory studies have been conducted to test porcine solid organs in humans, representing a new step in moving xenotransplantation towards clinical application. These studies are summarized below and attracted wide interest in the media and scientific community, resulting in commentaries in scientific journals (referenced below). We focus in this commentary on safety, that is, the potential of transspecies transmission of infectious agents, in particular viruses.1 Transspecies transmission of endogenous retrovirus, that is, porcineendogenous retrovirus (PERV)hasbeen subject of much research during the last decades; this research resulted, amongst others, in studies using pig donors that are negative for the PERV-C subtype, or in generation of pigs in which PERV-A and PERV-B subtypes were genetically inactivated (on a PERV-C negative platform).2 Although PERV-C infects only pig cells but not human cells, its presence allows recombination between PERV-C and PERV-A, resulting in high titer PERV-A/C recombinants.3 However, such a recombination is a rare event in vivo.4 The item of PERV risk was not addressed in the exploratory studies, and will not be discussed in this manuscript. But, one exogenous virus, porcine cytomegalovirus (PCMV), popped up in