Promotive effect of macrophage colony-stimulating factor on long-term engraftment of murine hematopoietic stem cells

• Published in: Cytokine (Philadelphia, Pa.) Pa.), 2005-09, Vol.31 (6), p.447-453
• Main Authors: Imada, Chiharu, Hasumura, Mai, Nawa, Katsuhiko
• Format: Article
• Language: English
• Subjects: Animals; c-Fms; Cell Proliferation; Cells, Cultured; Colony-Forming Units Assay; Ex vivo expansion; Hematopoietic stem cells; Hematopoietic Stem Cells - drug effects; Hematopoietic Stem Cells - physiology; Interleukins; Long-term repopulation; M-CSF; Macrophage Colony-Stimulating Factor - pharmacology; Mice; Mice, Inbred C57BL; Receptor, Macrophage Colony-Stimulating Factor - genetics; Receptor, Macrophage Colony-Stimulating Factor - metabolism; RNA, Messenger - metabolism
• ISSN: 1043-4666; 1096-0023
• DOI: 10.1016/j.cyto.2005.07.001

Large ex vivo expansion of hematopoietic stem cells (HSCs) sufficient for use in clinical applications has not been achieved, although the influence of some cytokines including SCF, IL-11, Flt3-L, and TPO for this purpose has been reported. We present evidence for an indirect effect of macrophage colony-stimulating factor (M-CSF) on expansion of murine HSCs. Fresh Lin −/low cells were isolated from Ly5.1 mouse bone marrow and cultured with or without M-CSF in the presence of SCF + IL-11 + Flt3-L or SCF + IL-11 + TPO for 6 days. The expanded cells were harvested and transplanted into lethally irradiated Ly5.2 recipients with competitor cells. Culture of Lin −/low cells with M-CSF significantly enhanced long-term engraftment. When the more enriched HSC populations of Lin −/low c-Kit + Sca-1 + cells were used as a source of HSCs, such a promotive effect was not observed, in agreement with negative expression of the M-CSF receptor (c-Fms). However, co-culture with Lin −/low c-Fms + resulted in a significant increase of long-term engraftment. These results suggested that M-CSF is an indirect stimulator for ex vivo expansion of HSCs in the presence of SCF, IL-11, Flt3-L, and TPO. These observations provide new directions for ex vivo expansion and insight into new engraftment regulation through M-CSF signaling.