HUMAN UMBILICAL-CORD BLOOD HEMATOPOIETIC PROGENITOR CELLS - ARE THEY THE SAME AS THEIR ADULT BONE-MARROW COUNTERPARTS

In an attempt to expand the hematopoietic progenitor cell (HPC) conten t of a single collection of umbilical cord blood (CB), we investigated the ex vivo proliferative potential of CB CD34(+) cells and the rate of exit of these cells from G(0)/G(1) phases of cell cycle in response to different cytokine combinations, Initial experiments in which phen otypically defined populations of CB and adult bone marrow (BM) CD34() cells were examined for their HPC content revealed that, contrary to BM, CB CD34(+) human leukocyte A (HLA)-DR(+) cells appeared to contai n the majority of primitive HPC. In cultures of BM CD34(+) HLA-DR(+) c ells incubated with stem cell factor (SCF) + interleukin-3 (IL-3), CD3 4(+) cells increased five-fold over 5 days, while CD34(+) cells from C B CD34(+) HLA-DR(+) cultures increased Ii-fold under these same condit ions, illustrating an enhanced proliferative potential of CB CD34(+) H LA-DR(+) cells vs, similar cells from adult BM. Furthermore, a 6.2-fol d increase in the number of CB CD34(+) still residing in G(0)/G(1) was observed on day 5 in cultures supplemented with SCF and IL-3, suggest ing the generation of large numbers of primitive HPC in vitro, The eff ect of SCF on the exit of CB and BM CD34(+) HLA-DR(+) cells from G(0)/ G(1) was then examined, Following 36- to 48-hour exposure to SCF, 45% of quiescent CB cells exited G(0)/G(1) in contrast to only 13% of quie scent BM cells, In serum-free media supplemented with either SCF or IL -3 alone, CB CD34(+) HLA-DR(+) cells did not exit G(0)/G(1) phases of cell cycle as rapidly as when CB plasma was present, unless SCF and IL -3 were added simultaneously. Collectively, these results suggest that CB CD34(+) cells are more responsive to cytokine stimulation, especia lly SCF, and may represent more suitable candidates for ex vivo expans ion of HPC than BM cells, Furthermore, these data illustrate potential ly important biologic differences between the HPC content of subpopula tions of BM and CB cells, and the response of these subpopulations to cytokine stimulation.