Effect of cytokine treatment (granulocyte colony-stimulating factor and stem cell factor) on hematopoiesis and the circulating pool of hematopoietic stem cells in mice.

The mobilization of hematopoietic stem cells (HSCs) into the peripheral blood of mice was induced by recombinant human granulocyte colony-stimulating factor (rhG-CSF) (250 microgram/kg/d) alone or combined with recombinant rat stem cell factor (rrSCF) (34 microgram/kg/d), injected subcutaneously (s.c.) once a day for 10 and 17 days. After administering G-CSF plus SCF or G-CSF alone for 10 days, the level of day-11 spleen colony-forming units (CFU-S-11) in the peripheral blood increased 169- and 93-fold, respectively. The effect was lower--30- and 17-fold--after 17 days of treatment. A 1.5- to three-fold decrease in CFU-S-11 content in the bone marrow of treated mice was observed. In normal mice, the content of long-term culture initiating cells (LTC-IC) in blood was below the threshold level. Cytokine treatment mobilized LTC-IC in the circulation. Following a 10- and 17-day course of G-CSF plus SCF, the proliferation of CFU-S-11 in the peripheral blood but not in the bone marrow increased from <10% in the controls to 44 and 72%, respectively, as measured by hydroxyurea (HU) suicide. Spleen-repopulating ability (SRA) of CFU-S (daughter CFU-S-8 content in an 11-day-old spleen colony) increased two-fold in the peripheral blood after a 10-day course and seven-fold after a 17-day course of combined cytokines. One month after the final cytokine injection, all hematopoietic indexes (including the number of different precursors, their proliferative rate, and their SRA) were near normal. The results suggest that the age structure of the mobilized progenitor population depends on both the cytokines used and the duration of the treatment: more immature CFU-S with higher proliferative activity and an increased SRA were mobilized preferentially after a 17-day course of combined cytokines.