HIGH-DOSES OF PURIFIED STEM-CELLS CAUSE EARLY HEMATOPOIETIC RECOVERY IN SYNGENEIC AND ALLOGENEIC HOSTS

In humans, autologous transplants derived from bone marrow (BM) usuall y engraft more slowly than transplants derived from mobilized peripher al blood. Allogeneic BM transplants show a further delay in engraftmen t and have an apparent requirement for donor T cells to facilitate eng raftment, In mice, Thy-1.1(lo)Lin(-/lo)Sca-1(+) hematopoietic stem cel ls (HSCs) are the principal population in BM which is responsible for engraftment in syngeneic hosts at radioprotective doses, and higher do ses of HSCs can radioprotect an allogeneic host in the absence of dono r T cells, Using the mouse as a preclinical model, we wished to test t o what ex:tent engraftment kinetics was a function of HSC content, and whether at high doses of c-Kit(+)Thy-1.1(lo)Lin(-/lo)Sca-1(+) (KTLS) cells rapid allogeneic engraftment could also be achieved, Here we dem onstrate that engraftment kinetics varied greatly over the range of KT LS doses tested (100-10,000 cells), with the most rapid engraftment be ing obtained with a dose of 5,000 or more syngeneic cells. Mobilized s plenic KTLS cells and the rhodamine 123(lo) subset of KTLS cells were also able to engraft rapidly, Higher doses of allogeneic cells were ne eded to produce equivalent engraftment kinetics. This suggests that in mice even fully allogeneic barriers can be traversed with high doses of HSCs, and that in humans it may be possible to obtain rapid engraft ment in an allogeneic context with clinically achievable doses of puri fied HSCs.