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Genetic Engineering of the Donor as an Approach to Clinical Xenotransplantation E. Cozzi, B. Soin, B. Holmes, and D. White ENOTRANSPLANTATION may provide a potential successful manipulation, pigs that express high levels of the X solution to the lack of human organs available for H-antigen and low levels of Gal epitopes have been transplantation. However, for xenotransplantation to be- obtained. In vivo data on transplantation of these organs come a clinical reality, the immunological mechanisms that into primates have yet to be published. underlie the rejection of xenografts must be controlled. However, at least two considerations suggest that this The recent elucidation of part of these immunological approach alone may not be sufficient to obtain long-term mechanisms, together with the advances in the field of survival of a xenograft. First, anti-Gal antibodies are only genetic engineering, has led to the production of transgenic one of the many aspects of the anti-pig immune response animals whose organs are less susceptible to the immuno- observed in primates. While this humoral immune response logical damage responsible for xenograft rejection. is certainly the most important prior to transplantation, one This article will briefly summarize the recent advances in cannot rule out that other specificities might become more this field. Particular attention will be placed on the pig-to- important once a primate is exposed to porcine tissues for primate model, since this species combination provides the long periods. Second, it has been suggested that in the most relevant model for clinical xenotransplantation. pig-to-primate combination, complement activation
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