A FUNCTIONAL COMPARISON OF CD34(+)CD38(-) CELLS IN CORD-BLOOD AND BONE-MARROW

We present cell cycling and functional evidence that the CD34(+)CD38(-) immunophenotype can be used to define a rare and primitive subpopulation of progenitor cells in umbilical cord blood. CD34(+)CD38(-) cells comprise 0.05% +/- 0.08% of the mononuclear cells present in cord blood. Cell cycle analysis with the fluorescent DNA stain 7-aminoactinomycin D showed that the percentage of CD34(+) cells in cycle directly correlated with increasing CD38 expression. CD34(+)CD38(-) cord blood cells were enriched for long-term culture-initiating cells (LTClC; cells able to generate colony-forming unit-cells [CFU-C] after 35 to 60 days of coculture with bone marrow stroma) relative to CD34(+)CD38(+) cells. In an extended LTClC assay, CD34(+)CD38(-) cells were able to generate CFUC between days 60 and 100, clearly distinguishing them from CD34(+)CD38(+) cells that did not generate CFU-C beyond day 40. When plated as single cells, onset of clonal proliferation was markedly delayed in a subpopulatidn of CD34(+)CD38(-) cells; clones (defined as > 100 cells) appeared after 60 days of culture in 2.9% of CD34(+)CD38(-) cells. In contrast, 100% of CD34(+)CD38(+) cells formed clones by day 21. Although the CD34(+)CD38(-) immunophenotype defines highly primitive populations in both bone marrow and cord blood, important functional differences exist between the two sources. CD34(+)CD38(-) cord blood cells have a higher cloning efficiency, proliferate more rapidly in response to cytokine stimulation, and generate approximately sevenfold more progeny than do their counterparts in bone marrow. (C) 1995 by The American Society of Hematology.