Xenotransplantation: Application of disease resistance

1. Organ transplantation is now clinically routine for patients with end-st age organ failure. One major limitation in transplantation is chronic rejec tion involving the loss of the graft despite the use of immunosuppressive a gents. Haematopoietic stem cell (HSC) chimerism, achieved through bone marr ow transplantation (BMT), induces donor-specific tolerance to transplanted organs and prevents chronic rejection. 2. A second major limitation to organ transplantation is the donor shortage . Xenotransplantation, the transplantation of organs between different spec ies, would have the ability to increase the availability of donor organs. 3. Current immunosuppressive therapies do not prevent the rejection of xeno grafts, Therefore, the only reliable method for achieving donor-specific to lerance to xenografts may require HSC chimerism, 4. In order to justify the use of BMT to induce transplantation tolerance i n patients with non-life-threatening diseases, the morbidity and mortality associated with current conditioning regimens must be addressed. 5. The use of partial conditioning regimens to promote engraftment of xenog eneic HSC and the development of donor-specific tolerance may eventually ma ke xenotransplantation in humans a clinical reality. 6. Additional advantages of xenotransplantation are the ability to genetica lly engineer the donor xenograft and resistance of some xenografts to infec tion by human viruses because of the species specificity of most viruses. 7. The clinical application of disease resistance for HIV and hepatitis B v irus is the focus of the present review.