Differential effects of recombinant human colony stimulating factor (rh G-CSF) on stem cells in marrow, spleen and peripheral blood in mice
British journal of haematology, 76 (2):
174–179 (1990)Abstract
Previously it has been hypothesized that the granulopoietic and erythropoietic lineages may compete for differentiating stem cells. According to this hypothesis one would expect that a stimulation of granulopoiesis by G-CSF administration would lead to a reduction of the stem cell pool and be followed by a decline of erythropoietic progenitor numbers. In addition one would expect an enhanced response of granulopoiesis if G-CSF administration were combined with suppression of erythropoiesis by red cell transfusion. To evaluate whether this hypothesis holds true C57bl mice were injected subcutaneously for 6 d with 3.75 micrograms rh G-CSF/mouse/d (150 micrograms G-CSF/kg body weight/d). Marrow CFU-S numbers showed an increase to 160\% on day 2, followed by a decrease to 50\% of control on day 6. Splenic and peripheral blood CFU-S increased 20-fold and 10-fold, respectively. Marrow CFU-E declined to 40\% of the control value. Splenic CFU-E increased 10-fold. The increase in marrow CFU-GM numbers ranged between 140\% and 180\%. CFU-GM obtained from the spleen and the peripheral blood increased 60-fold and 15-fold, respectively. Regarding the CFU-S and CFU-GM a similar pattern of response was found in an experiment where rh G-CSF administration was combined with an additional red cell transfusion. These data do not provide convincing evidence for an exhaustion of haemopoietic stem cells during treatment with G-CSF. They rather suggest that an important side effect of G-CSF treatment is a release of CFU-S and progenitors from the marrow to the peripheral blood and a reseeding in the spleen.