CD34⁺⁺CD38^- and CD34⁺CD38⁺ human hematopoietic progenitors from fetal liver, cord blood, and adult bone marrow respond differently to hematopoietic cytokines depending on the ontogenic source

CD34⁺⁺CD38^- and CD34⁺CD38⁺ hematopoietic progenitor cells (HPCs) 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 hematopoiesis, interferon (IFN)-γ and macrophage inflammatory protein (MIP)-1α. We observed first that a significantly lower percentage of CD34⁺⁺ cells were CD38^- in ABM than in FL and CB. Second, the functional differences between CD34⁺⁺CD38^- and CD34⁺CD38⁺ cells were less pronounced in FL and CB than in their ABM counterparts. Third, an inverse correlation was found between growth factor response and the ontogenic age of HPCs, and a direct correlation was noted between cytokine requirements and the ontogenic age of HPCs. Fourth, spontaneous colony formation in a classic semisolid culture system was reproducibly obtained only in the ontogenically earliest cells, that is, in FL but not in CB and ABM, in which no such spontaneous colony formation was observed. Fifth, the modulatory effects of IFN-γ and MIP-1α were qualitatively different depending on the ontogenic age of the progenitor source: whereas IFN-γ was only a selective inhibitor of primitive CD34⁺⁺CD38^- ABM progenitor cells, it inhibited both CD34⁺⁺CD38^-and CD34⁺CD38⁺ FL and CB cells to the same extent. In contrast to the effects of MIP-1α on ABM, we could not find any consistently stimulatory or inhibitory effects on FL and CB progenitors. 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 preparative protocols of ex vivo expansion, transplantation strategies, or gene transfer experiments.