Differential effects of recombinant human colony stimulating factor (rh G‐CSF) on stem cells in marrow, spleen and peripheral blood in mice

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.

Identification of CD13+CD36+ cells as a common progenitor for erythroid and myeloid lineages in human bone marrow

“…Our data showed that the proliferation and differentiation of erythroid and myeloid phenotypes could be induced from the same source of CD133 + cells, which is consistent with the effects of these cytokines on hematopoiesis [41,42]. Our observation of semi-solid cultures allows us to directly monitor the effect of EPO and G-CSF on the myeloid and erythroid lineage branching-point.…”

Transplantation of Allogeneic Peripheral Blood Stem Cells Mobilized by Recombinant Human Granulocyte Colony Stimulating Factor

“…M-CSF = Macrophage-Colony Stimulating Factor; IL-2 = Interleukin 2; IL-6 = Interleukin 6; G-CSF = Granulocyte-Colony Stimulating Factor. In murine models, stem cell factor (SCF) and G-CSF or a combination of the two increases the concentration of colony forming units-spleen (CFU-S) in the peripheral blood [32][33][34][35][36][37]. In the mouse, IL-8 also mobilizes PBSC which have long-term marrow repopulating ability [38].…”

Identification of a genetic locus modulating splenomegaly induced by granulocyte colony-stimulating factor in mice

“…In some experiments G-CSF 200 g/kg/day was used. We and others have previously reported [12][13][14][15][16] that at Leukemia these dosages of G-CSF, mice demonstrate similar neutrophilia and progenitor cell mobilisation to that observed in normal humans receiving 5-10 g/kg/day for 5 days. 2 The daily dose was given in two divided doses at 8 am and 6-7 pm each day, and blood and tissues harvested on the morning of the sixth day, 15 h after the final injection.…”

“…In contrast, splenic enlargement is a predictable and prominent in vivo response in mice injected with G-CSF. [12][13][14][15] Splenomegaly is due to increased extramedullary haemopoiesis in both species, but varies between species in relative extent. [11][12][13][14] In mice injected with G-CSF, spleen weight increases in parallel with nucleated cell number, 15 with the increased cellularity directly reflecting the dramatic expansion of splenic myelopoiesis.…”

“…[12][13][14][15] Splenomegaly is due to increased extramedullary haemopoiesis in both species, but varies between species in relative extent. [11][12][13][14] In mice injected with G-CSF, spleen weight increases in parallel with nucleated cell number, 15 with the increased cellularity directly reflecting the dramatic expansion of splenic myelopoiesis. 12,15,16 A possible explanation for the variation observed between normal subjects in regard in vivo responses to G-CSF such as splenic enlargement or progenitor cell mobilisation may lie in genetic differences in key systems or steps involved in each process.…”