Introduction: The Present Status of Xenotransplantation Research

There is a well-known worldwide shortage of deceased human donor organs for clinical transplantation. The transplantation of organs from genetically engineered pigs may prove an alternative solution. In the past 5 years, there have been sequential advances that have significantly increased pig graft survival in nonhuman primates. This progress has been associated with (1) the availability of increasingly sophisticated genetically engineered pigs; (2) the introduction of novel immunosuppressive agents, particularly those that block the second T-cell signal (costimulation blockade); (3) a better understanding of the inflammatory response to pig xenografts; and (4) increasing experience in the management of nonhuman primates with pig organ or cell grafts. The range of investigations required in experimental studies has increased. The standard immunologic assays are still carried out, but increasingly investigations aimed toward other pathobiologic barriers (e.g., coagulation dysregulation and inflammation) have become more important in determining injury to the graft. Now that prolonged graft survival, extending to months or even years, is increasingly being obtained, the function of the grafts can be more reliably assessed. If the source pigs are bred and housed under biosecure isolation conditions, and weaned early from the sow, most microorganisms can be eradicated from the herd. The potential risk of porcine endogenous retrovirus (PERV) infection remains unknown, but is probably small. Attention is being directed toward the selection of patients for the first clinical trials of xenotransplantation.