Transplantation tolerance and mixed chimerism: at the frontier of clinicalapplication

Although the persistence of donor-type hematopoietic cells in low numbers ( microchimerism) is well established in some transplant recipients, its rele vance for graft acceptance is still a matter of debate. On the other hand, clonal deletion of donor-specific alloreactive cells associated with mixed chimerism (macrochimerism) has reliably produced long-term graft tolerance in pre-clinical models. So far, the cytoablative conditioning regimens requ ired to achieve mixed chimerism have hampered the clinical development of s uch protocols. Here, we discuss recent observations suggesting that the del iberate induction of hematopoietic cell chimerism might become a feasible s trategy to achieve transplantation tolerance in clinics.