High doses of purified stem cells cause early hematopoietic recovery in syngeneic and allogeneic hosts.

In humans, autologous transplants derived from bone marrow (BM) usually engraft more slowly than transplants derived from mobilized peripheral blood. Allogeneic BM transplants show a further delay in engraftment and have an apparent requirement for donor T cells to facilitate engraftment. In mice, Thy-1.1 lo Lin /lo Sca-1 hematopoietic stem cells (HSCs) are the principal population in BM which is responsible for engraftment in syngeneic hosts at radioprotective doses, and higher doses of HSCs can radioprotect an allogeneic host in the absence of donor T cells. Using the mouse as a preclinical model, we wished to test to what extent 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 demonstrate that engraftment kinetics varied greatly over the range of KTLS doses tested (100-10,000 cells), with the most rapid engraftment being obtained with a dose of 5,000 or more syngeneic cells. Mobilized splenic KTLS cells and the rhodamine 123 lo subset of KTLS cells were also able to engraft rapidly. Higher doses of allogeneic cells were needed 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 engraftment in an allogeneic context with clinically achievable doses of purified HSCs. ( J. Clin. Invest. 1998. 101:961-966.) Key words: hematopoietic stem cell transplantation hematopoiesis mobilized peripheral blood We previously transplanted 10 6 BM cells (which contain 500 TLS cells) in comparison with 500 purified TLS cells, and the recovery kinetics of white blood cells (WBC), platelets, and hematocrit were essentially indistinguishable (5). Here we transplanted higher doses of BM KTLS cells or mobilized KTLS cells; these high doses lead to dramatically reduced engraftment times. Even a primitive HSC subset was capable of rapid engraftment. These results contradict the notion that purified HSC are incapable of early engraftment, and provide a basis for understanding the efficacy of MPB transplants.