CD34(-) AND CD34(+)CD38(+) HUMAN HEMATOPOIETIC PROGENITORS FROM FETALLIVER, CORD-BLOOD, AND ADULT BONE-MARROW RESPOND DIFFERENTLY TO HEMATOPOIETIC CYTOKINES DEPENDING ON THE ONTOGENIC SOURCE(+)CD38()

CD34(++)CD38(-) and CD34(+)CD38(+) hematopoietic progenitor cells (HPC s) from human fetal liver (FL), cord blood (CB), and adult bone marrow (ABM) were isolated and investigated for their growth characteristics , cytokine requirements and response to two modulators of early hemato poiesis, interferon (IFN)-gamma and macrophage inflammatory protein (M IP)-1 alpha. We observed first that a significantly lower percentage o f CD34(++) cells were CD38(-) in ABM than in FL and CB. Second, the fu nctional differences between CD34(++)CD38(-) and CD34(+)CD38(+) cells were less pronounced in FL and CB than in their ABM counterparts. Thir d, an inverse correlation was found between growth factor response and the ontogenic age of KPCs, and a direct correlation was noted between cytokine requirements and the ontogenic age of HPCs. Fourth, spontane ous colony formation in a classic semisolid culture system was reprodu cibly obtained only in the ontogenically earliest cells, that is, in F L but not in CB and ABM, in which no such spontaneous colony formation was observed. Fifth, the modulatory effects of IFN-gamma and MIP-1 al pha were qualitatively different depending on the ontogenic age of the progenitor source: whereas IFN-gamma was only a selective inhibitor o f primitive CD34(++)CD38(-) ABM progenitor cells, it inhibited both CD 34(++)CD38(-) and CD34(+)CD38(+) FL and CB cells to the same extent. I n contrast to the effects of MIP-1 alpha on ABM, we could not find any consistently stimulatory or inhibitory effects on FL and CB progenito rs. In conclusion, important functional and biologic differences exist between FL, CB, and ABM progenitor cells, and these differences could have major implications for the use of these cell populations in prep arative protocols of ex vivo expansion, transplantation strategies, or gene transfer experiments.