Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
9110816 | Cytokine | 2005 | 7 Pages |
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 Linâ/low cells were isolated from Ly5.1 mouse bone marrow and cultured with or without M-CSF in the presence of SCFÂ +Â IL-11Â +Â Flt3-L or SCFÂ +Â IL-11Â +Â TPO for 6 days. The expanded cells were harvested and transplanted into lethally irradiated Ly5.2 recipients with competitor cells. Culture of Linâ/low cells with M-CSF significantly enhanced long-term engraftment. When the more enriched HSC populations of Linâ/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 Linâ/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.
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Authors
Chiharu Imada, Mai Hasumura, Katsuhiko Nawa,