STRATEGIES FOR PREVENTING PORCINE XENOGRAFT REJECTION - RECENT PROGRESS AND FUTURE-DEVELOPMENTS

Interest in xenotransplantation (the use of animal organs for transpla ntation) has been revived because of the severe shortage of human dono r organs, and pigs are currently thought to be the species most suitab le 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 des igned to inhibit immune-mediated xenograft rejection. The first clinic al trials of porcine organs are expected within the next few years, on ce outstanding questions about the safety of transplanted pig tissues have been addressed. They will herald a new era in medical practice, c haracterised by the practical application of modern molecular and gene tic 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 inhi bit the progress of chronic rejection, the process that currently limi ts the lifespan of transplanted allografts. This article reviews the p athophysiology of xenograft rejection and highlights the novel strateg ies to prevent hyperacute xenograft rejection that are likely to be us eful in clinical practice. Other strategies designed to inhibit later stages of xenograft rejection are also presented, with emphasis on the need for graft-specific of 'tailored' immunosuppression. Areas where future development is likely are also discussed.