Future prospects

The two major problems in organ transplantation are:

Chronic graft rejection and the side effects of  

     nonspecific immunosuppression

  the shortage of organs for transplantation.

A long-standing goal in organ transplantation has been the development of strategies for inducing specific immunological tolerance. Transplantation tolerance would eliminate the need for long-term nonspecific immunosuppressive agents, leaving the immune system intact for defence against infec­tion. It has long been possible to induce transplant tolerance in experimental animals by a variety of preconditioning regimens that often involve antigen pretreatment schedules. So far, however, there is no clinically applicable strategy for inducing transplant tolerance.

The demand for human organs for transplantation is so great that cadaveric donors cannot ever satisfy it. Many consider that the solution is to perfect xenotransplantation, and there is general agreement that the pig is the most suitable source of xenogeneic organs. However, all humans have preformed antibodies directed against carbohydrate antigens expressed by pig organs and these result in hyperacute rejection. The dominant carbohydrate antigen responsible is galcL-1,3-gal. Progress has been made towards circumventing hyperacute xenograft rejection, for example by using organs from pigs that have been made transgenic for human complement regulatory proteins. However, such organs are still rejected within a few weeks by primates, despite the use of potent immunosuppressive agents. In addition to the complex immunological problems posed by xenotransplantation, there is a risk that pig organs may transmit infectious agents, and there is particular concern about the risks posed by porcine endogenous retrovirus (PERV). Finally, there are unanswered questions regarding the extent to which pig organs are able to fulfil the physiological demands required of them after transplantation into a human.