**3. Xenotransplantation**

Xenotransplantation, not a new concept in this field, is a controversial issue. Xenotransplantation which means transplantation of an organ, tissue, or cells between two different species, has regained attention because of advantages such as rich source, the chance of planned, and multiple transplantations. The main disadvantages are the possibility of animal disease transmission, immunologic, and physiologic differences.

In the sixteenth- century animal blood has been transferred to humans. Skin, corneal and blood vessel xenotransplantations were the early attempts. The kidney was the first solid organ of xenotransplantation. Dr. Keith Reemtsma, working at Tulane University, performed 13 xenotransplants in the 1960's using both chimpanzee kidneys on each surgery. Only one patient survived for nine months while the rest died within 4 to 8 weeks due to either infection or rejection. Dr. Thomas Starzl performed the first liver xenotransplant using baboons as donors [3].

In October 1984, orthotopic cardiac xenotransplantation on " Baby Fae" was performed by Dr. Leonard Bailey and his co-workers. The recipient was a 12-day neonate harboring hypoplastic left heart syndrome. The donor was an immunologically-selected baboon. The baby died on the 20th postoperative day. Neither humoral nor cellular rejection of the xenograft was noted [4].

Galactosyl-α-1-3, galactose [GAL] is the most important antigen in xenotransplantation. GAL is expressed in most cells of all mammals except humans, including porcine. GAL is found in intestinal bacteria, and there are antibodies against GAL in humans. Antibodies to nonGAL antigens are still a problem. The primary methods to prevent hyperacute rejection are the elimination of antibodies by plasmapheresis and immunoadsorption and depletion or inhibition of complements [5]**.**

In the last 30 years, researchers have determined that the pig is the most suitable animal for xenotransplantation. The reasons for this are short maturation time, the human similarity in size and physiological aspects, and low risk of animal disease transmission. Genetically modified pigs have been developed to overcome the molecular incompatibility between species. Another important step is the development of "knockout" pigs lacking the 1,3 galactosyl transferase gene encoding enzymes responsible for immunologic expression. Genetic engineering techniques can be easily applied to create rejection-resistant pig organs [6].

Knockout pigs have contributed to prolonged survival particularly in heart and kidney transplantation. Survival of pig-to-nonhuman primate heterotopic heart, kidney, and islet xenotransplantation over 900 days, over 400 days, and over 600 days respectively has been reported [7]. Bioartificial organs that contain pig cells or tissues have gained considerable clinical experience and the risks have been reduced [8]**.** For the time being, the indications of xenografting seem unclear but should be kept aside for exceptional cases.
