Xenotransplantation

Abstract

Purpose of review To review the progress in the field of xenotransplantation with special attention to most recent encouraging findings which will eventually bring xenotransplantation to the clinic in the near future. Recent findings Starting from early 2000, with the introduction of Gal-knockout pigs, prolonged survival especially in heart and kidney xenotransplantation was recorded. However, remaining antibody barriers to nonGal antigens continue to be the hurdle to overcome. The production of genetically-engineered pigs was difficult requiring prolonged time. However, advances in gene editing, such as zinc finger nucleases, transcription activator-like effector nucleases, and most recently CRISPR technology made the production of genetically-engineered pigs easier and available to more researchers. Today, the survival of pig-to-nonhuman primate heterotopic heart, kidney, and islet xenotransplantation reached >900 days, >400 days, and >600 day, respectively. The availability of multiple-gene pigs (5 or 6 genetic modifications) and/or newer costimulation blockade agents significantly contributed to this success. Now, the field is getting ready for clinical trials with an international consensus. Summary Clinical trials in cellular or solid organ xenotransplantation are getting closer with convincing preclinical data from many centers. The next decade will show us new achievements and additional barriers in clinical xenotransplantation.

High-mannose type N-glycans with core fucosylation and complex-type N-glycans with terminal neuraminic acid residues are unique to porcine islets

“…Though highly effective, the applicability of islet transplantation is limited by the shortage of human donor pancreases. Porcine donors are a promising alternative source of islets in light of their similar physiology and size compared with humans, their high reproductive capacity, and the potential for genetic manipulation [3,4]. Preclinical studies and initial clinical trials of islet xenotransplantation have demonstrated both the safety of porcine islet cell products and the need for developing new and improved startegies for preventing their rejection [5][6][7][8][9][10][11][12][13][14][15][16].…”

The major histocompatibility complex homozygous inbred Babraham pig as a resource for veterinary and translational medicine

“…In addition, the similarities in physiology and organ size mean that pigs are an excellent disease model with the potential to provide organs for human transplantation. 4,5 To enable future disease, vaccine and translational research, a more detailed understanding of the genetic variation that underpins differential immune responses in pigs is essential. Domesticated pigs have maintained a significant level of genetic diversity, both within and between breeds, despite strong selection for production traits and inbreeding.…”

The Past, Present and Future of Heart Transplantation

“…Today, the survival of pig-to-nonhuman primate heterotopic heart xenotransplantation has reached 945 days. 99) This required higher-than-standard immunosuppression therapy, including maintenance with anti-CD40 antibody. However, survival of orthotopic pig to nonhuman primate HTx grafts has so far been limited to less than 2 months, mostly as a result of perioperative cardiac xenograft dysfunction, which is believed to be distinct from acute rejection.…”