Xenotransplantation: how to overcome the complement obstacle?

The xenotransplantation research is driven by the shortage of allografts fo r transplantation of patients with end-stage organ failure and by lack of s uccess in developing suitable artificial organs. Pigs are now generally acc epted to be the donor species of choice, although a possible risk for trans mission of xenozoonoses, particularly pig endogenous retroviruses, should b e born in mind. A vascular xenograft from pig to human is usually rejected hyperacutely due to naturally occurring antibodies and complement. This hyp eracute rejection can be prevented by manipulating with either of these sys tems. In this review we briefly describe the hyperacute rejection and how i t can be prevented by complement modulation. Pigs made transgenic for human complement regulatory proteins seem very promising for future clinical exp eriments. Control of fluid-phase complement activation should be obtained a s well. The latter is discussed based on our own recent studies in this fie ld. (C) 1999 Elsevier Science Ltd. All rights reserved.