title: Promotive effect of macrophage colony-stimulating factor on long-term engraftment of murine hematopoietic stem cells.
abstract: 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.
authors.affiliation: Discovery Research Laboratory, Daiichi Pharmaceutical Company Limited, Kita-Kasai, Edogawa, Tokyo, Japan.
authors.forename: Chiharu
authors.initials: C
authors.lastname: Imada
authors.forename: Mai
authors.initials: M
authors.lastname: Hasumura
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Nawa
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000502:physiology; D007378:Interleukins; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000378:metabolism; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism*
chemical_list: D007378:Interleukins; D012333:RNA, Messenger; D016173:Macrophage Colony-Stimulating Factor; D016186:Receptor, Macrophage Colony-Stimulating Factor