In vivo stimulatory effect of macrophage colony-stimulating factor on the number of stroma-initiating cells

Abstract

The in vivo effect of human macrophage colony-stimulating factor (M-CSF) on the number of cells that formed stromal colonies in an in vitro culture system (stroma-initiating cells; SICs) was investigated. We found that the number of SICs in the femurs of C57BL/6 mice was significantly increased by the treatment with M-CSF. We also found that the SICs were resistant to at least three different chemotherapeutic reagents, 5-fluorouracil (5-FU), cytarabine, and cyclophosphamide, because the femoral cells of mice treated with these reagents contained higher numbers of SICs than those of untreated mice. M-CSF treatment also increased the number of SICs of the reagent-pretreated mice. The SICs detected in our culture system were present only in Mac-1(-)CD45(-) cells, and the M-CSF treatment of 5-FU-pretreated mice actually increased the number of Mac-1(-)CD45(-) SICs. The Mac-1(-)CD45(-) SICs collected from mice that were pretreated with 5-FU and then treated with M-CSF formed stromal colonies under in vitro culture conditions that did not contain M-CSF but did contain a high concentration of fetal calf serum. This result suggested that SICs collected following the treatment procedure did not necessarily require the presence of M-CSF for their in vitro proliferation. Our study indicated that M-CSF has the ability to increase the number of progenitor or precursor cells for bone marrow stromal cells in vivo system.

Effect of cytokines on the proliferation/differentiation of stroma-initiating cells

“…Although the treatment of mice with 5-FU markedly reduces the number of myeloid and lymphoid cells and their precursors (Hodgson and Bradley, 1979;van Zant, 1984;MullerSieburg, 1991), both SIC and CFU-F are resistant to the marrow ablating drug (Piersma et al, 1985;Deryugina et al, 1995;Tanaka-Douzono et al, 1999). However, SIC are not identical to CFU-F: CFU-F adhere to plastic dishes within 1 to 2 hr (Friedenstein et al, 1971;Castro-Malaspina et al, 1980;Piersma et al, 1985), whereas SIC are recovered in the nonadherent population (Deryugina et al, 1995;Yamada et al, 1997).…”

“…In an earlier study, we demonstrated the in vivo stimulatory effect of M-CSF on the number of SIC (Tanaka-Douzono et al, 1999). This was based on the findings that the administration of M-CSF to normal mice or myelosuppressed mice preinjected with anticancer drugs, including 5-FU, increased the number of SIC present in the bone marrow (Tanaka-Douzono et al, 1999).…”

“…The bone marrow cells were separated into subpopulations by a magnetic cell sorting system (MACS) (Tanaka-Douzono et al, 1999). The single-cell suspensions from femoral bone marrow cells were incubated with a cocktail of monoclonal antibodies specific to lineage markers (Mac-1, Gr-1, B220, Ly-1, and TER119) (Enrichment Cocktail for Murine Hematopoietic Progenitors, StemCell Technologies, British Columbia, Canada).…”

“…We also showed that the fibroblastic cells developed by M-CSF stimulation were functional stromal cells and that M-CSF had an ability to increase the number of the SIC in vivo (Tanaka-Douzono et al, 1999). The results raise the possibility that M-CSF modulates the proliferation or differentiation of the precursor of bone marrow fibroblastic stromal cells.…”

Macrophage Colony‐stimulating Factor (M‐CSF) Prevents Infectious Death Induced by Chemotherapy in Mice, While Granulocyte‐CSF Does Not

“…46) Further, M-CSF was suggested to have the ability to increase the number of progenitor or precursor cells for bone marrow stromal cells in vivo. 47) Based on these findings, M-CSF may have increased the production of some chemokines by monocytes in mice, enhancing the granulocyte function.…”