Xenotransplantation: Transplantable Transgenic Animal Organs

Xenotransplantation: Transplantable Transgenic Animal Organs

An innovative use of transgenics for the production of useful proteins is the generation of clinically transplantable transgenic animal organs. The success of human-to-human transplantation of heart, kidney, liver, and other vascularized organs (allotransplan-tation) created the significant expectation and need for donor organs. Primate-to-human transplantation (xenotransplantation was successful, but ethical issues and limited number of donor animals were significant barriers. Transplant surgeons recognized early on that organs from the pig were a rational choice for xenotransplantation (due to physiological, anatomical, ethical, and supply reasons) if the serious hyperacute rejection could be overcome. Several research groups in academia and industry have pioneered the transgenic engineering of pigs expressing both human complement inhibitory proteins as well as key human blood group proteins (antigens) (Makowka, 1993; Fodor et al., 1994; McCurry et al., 1995; Saadi and Platt, 1997; Dunn et al., 2005). Cloning has now produced transgenic pigs for xenotransplantation. Cells, tissues and organs from these double transgenic animals appear to be very resistant to the humoral immune system mediated reactions of both primates and likely humans. These findings begin to pave the way for potential xenograft transplantation of animalcomponents into humans with a lessened chance of acute rejection.