Comparison of the hematopoietic activity of flt-3 ligand and granulocyte-macrophage colony-stimulating factor acting alone or in combination

The hematopoietic sequelae of intramuscular administration of flt-3 ligand (FL) and granulocyte-macrophage colony-stimulating factor (GM-CSF) alone, o r in combination, were compared in BALB/c mice. Changes in hematopoiesis we re measured in the marrow, spleen and blood using an in vitro colony-formin g unit (CFU) assay and flow cytometrically (expression of CD34 and stem cel l antigen (Sca)-1). FL administration was associated with a significant inc rease in the absolute number of CFU and CD34(+) cells in the marrow and CFU , CD34(+), Sca-1(+), and CD34(+) Sca-1(+) cells in the spleen and blood. Th ese data demonstrate that FL expands and mobilizes a range of hematopoietic progenitors. By comparison, GM-CSF administration was associated with a si gnificant increase in the number of CFU in the spleen and a significant red uction in marrow CD34(+), Sca-1(+), and CD34(+) Sca-1(+) cells. These data suggest that GM-CSF-driven expansion of CFU may be at the expense of more p rimitive cells. The pattern of progenitor cell expansion associated with FL + GM-CSF administration was similar to that of FL alone with the following exceptions. The numbers of spleen and blood CFU were significantly greater and the number of marrow CD34(+) Sca-1(+) cells were significantly less, t han with FL alone. These data suggest that co-administration of these cytok ines may combine the expansion of the more primitive cell populations (asso ciated with FL) with the expansion of the more mature CFU population (assoc iated with GM-CSF) to yield a greater overall CFU expansion and elevation o f CFU in the blood. However, increasing the expansion and mobilization of t he relatively mature, rather than the more primitive, hematopoietic progeni tors, may be of limited value as a mobilization strategy, if the goal is th e expansion and isolation of increased numbers of "high-quality," primitive cells for transplantation.