Xenotransplantation

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Xenotransplantation

• Transplant of organs/tissues from one animal
  species into another

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Types of transplants

• Autograft (self to self)
• Isograft (from genetically identical individual)
• Allograft (from genetically non-identical member
  of same species)
• Xenograft (from one species to another)

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Concerns with xenografts

• Hyperacute rejection
• Later immunological problems
• Risks, especially infectious
• Ethical issues
• Use of animals, especially GM
• Creation of new transmissible disease

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Xenotransplantation

• History
• Blood transfusions in early 17thC
• Solid organ transplants in 20thC (chimpanzee
  kidney, use of immunosuppression, failure with
  other species as donors)
• Cell transplants some success (porcine islet
  cells)

• Shortfall in supply (UK figures for 2001)
• Waiting list 6842
• Donors 777
• Transplants 2339
• Shortfall 4503

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Potential donor species

• Chimpanzee
• Pigs
• Appropriate size
• Already bred for slaughter
• Extensive knowledge of husbandry and infectious
  diseases
• Transgenic and knockout pigs available
• Phylogenetic distance reduces risk of infectious
  diseases

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Potential donor species

• Lifespan differences?
• Continuing growth of organs from young donors?
• Cross species compatibility of produced hormones
  (insulin, renin?, erythropoietin?)
• Body temperature (37º versus 39º)

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Associated problems

• Hyperacute rejection
• Xenoreactive natural antibodies in recipient
  against the gal epitope on cells of non-primate
  species
• Generated in response to gut microbes that have
  epitope on surface
• Act by complement activation and NK cells

• Later immunological problems
• Acute (24hrs) rejection due to IgM and IgG
  anti-gal leading to DIC
• CMI rejection

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Associated problems

• Risks
• Infectious agents
• PERVS (porcine endogenous retroviruses), can
  infect human cells in vitro and mice in vivo.
• Theoretical generation of pathogenic,
  replication- competent, exogenous retrovirus

• Assessing and reducing the risk
• Long history of using porcine heart valves and
  insulin
• Eliminate known agents from donor herd
• No PERV transmission in 160 pig cell recipients

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Ethical issues

• Producing Frankenstein creatures
• Choice of donor species (Speciesism)
• Health and welfare of donors (particularly GM
  donors)
• Risk of generating new infectious pathogen
  (save individual but risk mankind)