Xenotransplantation

David KC Cooper, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
Burcin Ekser, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
Mohamed Ezzelarab, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
Hidetaka Hara, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

Published online: December 2012

DOI: 10.1002/9780470015902.a0001249.pub3

The transplantation of organs and tissues across species is called xenotransplantation. The most likely source of animal organs and cells for transplantation into humans is the pig. Pigs, therefore, have been genetically engineered to provide their tissues with some protection against the human immune response. The classical ‘rejection’ of pig organs has largely been overcome, but thromboses (clots) occur in the small blood vessels of the graft. Pigs with human ‘antithrombotic’ genes are now becoming available and it is hoped will prevent this complication. Hearts from genetically engineered pigs have functioned in nonhuman primates for up to 8 months, and pig pancreatic islets (that produce insulin) have controlled diabetes in monkeys for longer than 1 year. The safety of xenotransplantation remains of some concern. Is there a risk of the transfer of a pig infectious microorganism into the community? Present evidence is that this potential risk is low. This potential, however, has legal and regulatory implications.

Key Concepts:

  • There is a critical shortage of organs from deceased humans for transplantation into patients with vital organ failure.
  • There are an estimated one and a half million people in the USA alone with Type 1 (juvenile) diabetes who might benefit by the transplantation of pancreatic islets (which secrete insulin).
  • Because of its anatomical and physiological similarities to humans, the pig is in many ways a suitable source of organs and cells for transplantation into patients.
  • Protection from the primate immune response can be achieved in pigs by genetic engineering, which largely consists of introducing into the pig one or more human ‘protective’ genes.
  • The major remaining problem appears to be a tendency for thromboses (clots) to form in the blood vessels of the pig organ graft, but it is hoped this will be resolved by the introduction of human ‘antithrombotic’ genes into the pig.
  • There is some concern that a pig infectious microorganism could be transferred to the human recipient of a pig organ and that this microorganism could be passed on to the recipient's contacts, but this risk is now considered to be low.
  • Clinical trials of pig organ and cell transplantation will need to be regulated by national regulatory agencies such as the FDA in the USA.

Keywords: xenotransplantation; organ transplantation; transplantation immunology; xenografts; rejection

Figure 1. Mythological animals that can be considered examples of xenotransplantation. (a) The chimaera. (b) The lamassu.
Figure 2. The increasing disparity between the number of patients on the waiting list for organ transplantation (squares) and the number of donor organs that became available (diamonds) in the USA between 1994 and 2011. Source: Data based on the United Network for Organ Sharing (UNOS) waiting list and transplantation files.
Figure 3. Drawing of human antipig antibodies binding to Gal (and non-Gal) carbohydrate antigens expressed on the pig vascular endothelial cells. This antibody–antigen interaction leads to activation of complement that causes injury to the endothelial cells and can result in hyperacute rejection.
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 References
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    Cooper DKC (2012) A brief history of cross-species organ transplantation. Baylor University Medical Center Proceedings 25(1): 49–57.
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    book Hammer C (1991) "Evolutionary, physiological, and immunological considerations in defining a suitable donor for man". In: Cooper DKC, Kemp E, Reemtsma K and White DJC (eds) Xenotransplantation: The Transplantation of Organs and Tissues between Species, pp. 429–438. Heidelberg: Springer.
    Hara H and Cooper DKC (2011) Xenotransplantation – the future of corneal transplantation? Cornea 30(4): 371–378.
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    Onions D, Cooper DKC, Alexander TJL et al. (2000) An assessment of the risk of xenozoonotic disease in pig-to-human xenotransplantation. Xenotransplantation 7(2): 143–155.
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    Robson SC, Cooper DKC and d'Apice AJF (2000) Disordered regulation of coagulation and platelet activation in xenotransplantation. Xenotransplantation 7(3): 166–176.
    Rose AG and Cooper DKC (2000) Venular thrombosis is the key event in the pathogenesis of antibody-mediated cardiac rejection. Xenotransplantation 7(1): 31–41.
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    Tseng Y-L, Sachs DH and Cooper DKC (2005) Porcine hematopoietic progenitor cell transplantation in nonhuman primates: a review of progress. Transplantation 79(1): 1–9.
 Further Reading
    book Advisory Group on the Ethics of Xenotransplantation (1996) Animal Tissues into Humans. Norwich: Her Majesty's Stationary Office (HMSO).
    Cooper DKC and Ayares D (2012) Potential benefits and risks of clinical xenotransplantation. Transplant Research and Risk Management 4(1): 7–17.
    book Department of Health and Human Services (1996) Draft Public Health Services (PHS). Guideline on Infectious Issues in Xenotransplantation. Washington DC: Public Health Services (PHS).
    book Institute of Medicine (1996) Xenotransplantation: Science, Ethics, and Public Policy. Washington DC: National Academy Press.
    Lanza RP, Cooper DKC and Chick WL (1997) Xenotransplantation. Scientific American 277(1): 54–59.
    Manji RA, Menkis AH, Ekser B and Cooper DKC (2012) Porcine bioprosthetic heart valves – the next generation. American Heart Journal 164(2): 177–185.
    book World Health Organization (1998) Xenotransplantation: Guidance on Infectious Disease Prevention and Management. Geneva: World Health Organization (WHO).

Related Sub-Topics:

Antibodies | Transplantation
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Article Title: Xenotransplantation
 
How to Cite close
Cooper, David KC, Ekser, Burcin, Ezzelarab, Mohamed, and Hara, Hidetaka(Dec 2012) Xenotransplantation. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001249.pub3]