Genetic diversity, growth and heart function of Auckland Island pigs, a potential source for organ xenotransplantation

Porcine endogenous retrovirus C (PERV-C) is a gammaretrovirus present in the genome of many, but not all pigs. PERV-C is an ecotropic virus, able to infect only pig cells. In contrast, PERV-A and PERV-B are present in all pigs, they can infect cells of numerous host species including humans, and therefore pose a risk for xenotransplantation using pigs as donor animals. Intriguingly, PERV-C can recombine with PERV-A and the resulting PERV-A/C recombinants can also infect human cells and replicate to higher titers compared to the paternal PERV-A. Therefore, only PERV-C-free animals should be used for xenotransplantation. When screening wild boars and German landrace pigs for PERV-C, proviral variants were detected, and to detect these variants, new PCR methods were developed. Furthermore, PERVs are known to be active in living pigs as demonstrated by recombination and by different copy numbers in various organs and different parts of an organ. Copy numbers also increased with the age of the animals. This data was obtained by PCR using primers amplifying the highly conserved polymerase sequence which is identical in PERV-A, PERV-B and PERV-C. Here we screened indigenous Greek black pigs, Auckland Island pigs and German slaughterhouse pigs for the presence of PERV-C, using different PCR-based methods and optimized these detection methods. Auckland Island pigs were PERV-C-negative and represent the optimal donor pigs after genetic modifications.

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Progress in Orthotopic Pig Heart Transplantation in Nonhuman Primates

Längin,

Bender,

Schmoeckel

et al. 2024

Transpl Int

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Xenotransplantation of porcine hearts has become a promising alternative to human allotransplantation, where organ demand still greatly surpasses organ availability. Before entering the clinic, however, feasibility of cardiac xenotransplantation needs to be proven, ideally in the life supporting orthotopic pig-to-nonhuman primate xenotransplantation model. In this review, we shortly outline the last three decades of research and then discuss in detail its most recent advances. These include the genetic modifications of donor pigs to overcome hyperacute rejection and coagulation dysregulation, new organ preservation methods to prevent perioperative xenograft dysfunction, experimental immunosuppressive and immunomodulatory therapies to inhibit the adaptive immune system and systemic inflammation in the recipient, growth control concepts to avoid detrimental overgrowth of the porcine hearts in nonhuman primates, and lastly, the avoidance of porcine cytomegalovirus infections in donor pigs. With these strategies, consistent survival of 6–9 months was achieved in the orthotopic xenotransplantation model, thereby fulfilling the prerequisites for the initiation of a clinical trial.

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Genetic diversity, growth and heart function of Auckland Island pigs, a potential source for organ xenotransplantation

Cited by 4 publications

References 64 publications

Xenotransplantation Literature Update December 2023–June 2024

Xenotransplantation Literature Update December 2023–June 2024

Screening for porcine endogenous retrovirus - C (PERV-C) in pigs

Progress in Orthotopic Pig Heart Transplantation in Nonhuman Primates

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