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

We present cell cycling and functional evidence that the CD34(+)CD38(- ) immunophenotype can be used to define a rare and primitive subpopula tion of progenitor cells in umbilical cord blood. CD34(+)CD38(-) cells comprise 0.05% +/- 0.08% of the mononuclear cells present in cord blo od. Cell cycle analysis with the fluorescent DNA stain 7-aminoactinomy cin D showed that the percentage of CD34(+) cells in cycle directly co rrelated with increasing CD38 expression. CD34(+)CD38(-) cord blood ce lls were enriched for long-term culture-initiating cells (LTClC; cells able to generate colony-forming unit-cells [CFU-C] after 35 to 60 day s of coculture with bone marrow stroma) relative to CD34(+)CD38(+) cel ls. In an extended LTClC assay, CD34(+)CD38(-) cells were able to gene rate CFUC between days 60 and 100, clearly distinguishing them from CD 34(+)CD38(+) cells that did not generate CFU-C beyond day 40. When pla ted as single cells, onset of clonal proliferation was markedly delaye d in a subpopulatidn of CD34(+)CD38(-) cells; clones (defined as > 100 cells) appeared after 60 days of culture in 2.9% of CD34(+)CD38(-) ce lls. 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 c ells have a higher cloning efficiency, proliferate more rapidly in res ponse to cytokine stimulation, and generate approximately sevenfold mo re progeny than do their counterparts in bone marrow. (C) 1995 by The American Society of Hematology.