01 June 2007

Interspecies Organ Transplants

Originating as early as the 1600’s it seems that xenotransplantation has always fascinated mankind. It is only recently however that it’s potential through porcine organs to solve the high demand and low supply of human organs, has come into light.

Although one cannot just simply put a pig organ into a human being and “hope for the best”. Three major hurdles must still be overcome. These include:

Immunological rejection by the host immune system,
The transfer of zoonotic agents such as brucellosis,
The size and physiological characteristics of the organ. ( Conquered by choice of an appropriate animal.)





Many techniques have been employed for immune modulation
in the recipient to improve the success of xenotransplantation,
overcoming the barriers summarised diagrammatically. However with current technology, it is now possible to alter the porcine genome aswell, thus evading the risks for infection, malignancy and drug toxicity. Two methods can be utilised here:
1. Alteration of the porcine genome to express no, or low
levels of antigens recognised by xenoreactive anti-bodies.
Specifically via the combination of an α1,2-fucosyltransferase encoding gene which encourages competitive glycosylation, plus an αgalactosidase gene,which removes the terminal αGal molecule.
2. The introduction of proteins such as CD59 to ensure the organs are protected from human complement activation.

Ethical and more notably animal welfare issues also exist within this field of study, however, with the first few barriers to xenotransplantation, already surmounted; it seems not long before a 400year old dream can become a reality.
References
Primary reference:
Platt,J.L.(2001).Xenotransplantation.Washington,DC: ASM Press.

Secondary references:
Combined transgenic expression of alpha-galactosidase and alpha1,2-fucosyltransferase leads to optimal reduction in the major xenoepitope Galalpha(1,3)Gal.(1997). Retrieved May 28, from http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9405672&dopt=Abstract

Françoise, A., et al.(2007). Xenotransfusions, past and present. Retrieved May 31,2007, from
http://www.blackwell-synergy.com/doi/abs/10.1111/j.1399-3089.2007.00404.x

McCarthy,A.(2005). Clinical Realities of Xenotransplantation and Cell Therapy.Retrieved May 24, 2007, from http://www.alicemccarthy.com/Articles/Advances%20in%20Xenotransplantation.htm

Homologous recombination. Retrieved May 29,2007, from
http://www.web-books.com/MoBio/Free/Ch8D1.htm

Materials and methods for management of hyperacute rejection in human xenotransplantation.(2007). Retrieved May 29,2007, from http://www.patentstorm.us/patents/7201899-fulltext.html

Promising advances in xenotransplantation.(2002). Retrieved May 30,2007, from http://www.vetscite.org/publish/items/000529/index.html
By Katherine Anne Cowling 41450466