Xenograft

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A Xenograft is defined as the transplantation of a tissue or whole organ across species[1].

The process has been done many times within research with xenografts between rats and mice common, however there are many problems surrounding the continued acceptance of a xenograft from a recipient. If these issues could be overcome then the possibilities are enourmous to both medicine and humanity as a whole; for one the crippling lack of donor organs would mean life to many on transplant waiting lists [2].

Obstacles In Xenograft Usage

There are a few key obstacles within xenograft usage. Namely they are;

  1. MHC Incompatibility And T-Cells
  2. Other, MinorAllo-antigens

Incompatibilities within the donor and recipient's Major and Minor Histocompatibility Complexes cause non-self specific T-cells to be activated that in turn activate the production of antibodies and the complement and clotting cascades against the graft (be it a xenograft or allograft, in this case the former.). Non-self specific T-cells are always produced by the immune system and as a result hemorrhaging of the Graft occurs rapidly [3]. MHC Incompatobility is not as much of a problem as it was in the past however, Immuno-suppressent drugs and more recently anti-CD4 and anti-CD8 monoclonal antibodies can be given to the recipient to overcome any MHC incompatibilities, thus prolonging the recipient's tolerance to the graft [4]. Anti-CD4 and anti-CD8 monoclonal antibodies have the added benefit of not suppressing the entirety of the recipient's immune system, as well as avoiding the need for T-cell depletion, so that the recipient is not vulnerable to oppurtunistic infections. However, T-cell mediated actions against a xenograft are still vastly complicated and, at the moment, untamed.

Other minor antigens, for example the mammalian ubiquitous carbohydrate antigen α-Gal, have natural antibodies opposing them within primates. Pigs, theorised to be the most similar in organ size to humans (as well as being already farmed and harvested for their meat), unfortunately also have these carbohydrate antigens. When a xenograft from a Pig is placed into a human recipient these natural antibodies bind to the minor antigens (such as α-Gal) and are the cause of swift, hyperacute rejection. Such as with MHC incompatibility there have been developments to overcoming these antigens, the production of transgenic pigs that express human minor antigens as well as the pig's natural α-Gal being a major step to overcoming this obstacle [5].

References

  1. Game, DS. (2001 ). Rejection mechanisms in transplantation.. Wien Klin Wochenschr.. 113 (20-21), 832-8.
  2. Murphy, K (2012). Janeway's Immunobiology. 8th ed. New York: Garland Sciences. p.657-658
  3. Murphy, K (2012). Janeway's Immunobiology. 8th ed. New York: Garland Sciences. p.652-654, 657
  4. Zonghua Chen. (1992). Tolerance in the mouse to major histocompatibility complex-mismatched heart allografts, and to rat heart xenografts, using monoclonal antibodies to CD4 and CD8. European Journal of Immunology. 22 (3), p805-810. DOI: 10.1002/eji.1830220326
  5. Murphy, K (2012). Janeway's Immunobiology. 8th ed. New York: Garland Sciences. p658

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