Donor-derived hematopoietic cells in organ transplantation: A major step toward allograft tolerance?

Infusion of donor-derived cells can improve organ allograft survival in animal models. Under certain conditions, it can even induce tolerance (i.e., unlimited organ survival without any maintenance immunosuppressive therapy): Use of nonmyeloablative regimens allows engraftment of donor-derived bone marrow cells, induction of mixed chimerism, and tolerance in rodents. High doses of bone marrow cells together with anti-T-cell antibodies can even result in mixed chimerism without cytoablative host conditioning. Cultured donor-derived CD34(+) cells or donor-derived immature (or even mature) dendritic cells associated with monoclonal antibodies directed against co-stimulatory molecules might also induce tolerance. Among the numerous experimental protocols leading to tolerance of solid organs in animal models, how can we find our bearings in human transplantation? Numerous problems have yet to be solved: the type and amount of donor-derived cells (including stromal cells) to be used, the timing for infusion of donor cells in keeping with organ transplantation, the route of infusion (should it be, intravenous, into the portal vein?), and the conditioning regimen. The first clinical trials would appear to indicate that tolerance induction in humans using donor-derived cells is a relatively safe solution that is both promising and realistic.