| Abstract: | Interest in xenotransplantation (the use of animal organs for transplantation) has been revived because of the severe shortage of human donor organs, and pigs are currently thought to be the species most suitable for widespread use. Recent insights into the mechanisms underlying vascular rejection, endothelial cell activation and cellular responses to xenogeneic tissue have led to the development of novel methods designed to inhibit immune-mediated xenograft rejection. The first clinical trials of porcine organs are expected within the next few years, once outstanding questions about the safety of transplanted pig tissues have been addressed. They will herald a new era in medical practice, characterised by the practical application of modern molecular and genetic techniques to solve clinical problems. In the future, it is hoped that these same techniques may resolve some of the problems currently associated with long-term systemic immunosuppression and serve to inhibit the progress of chronic rejection, the process that currently limits the lifespan of transplanted allografts. This article reviews the pathophysiology of xenograft rejection and highlights the novel strategies to prevent hyperacute xenograft rejection that are likely to be useful in clinical practice. Other strategies designed to inhibit later stages of xenograft rejection are also presented, with emphasis on the need for graft-specific or ‘tailored’ immunosuppression. Areas where future development is likely are also discussed. |
