N. Uchida et al., HIGH-DOSES OF PURIFIED STEM-CELLS CAUSE EARLY HEMATOPOIETIC RECOVERY IN SYNGENEIC AND ALLOGENEIC HOSTS, The Journal of clinical investigation, 101(5), 1998, pp. 961-966
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.