In vivo stimulatory effect of macrophage colony-stimulating factor on the number of stroma-initiating cells.
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.
Biochemical Research Laboratory, Morinaga Milk Industry Co., Ltd., Zama, Kanagawa, Japan.
M
M
Tanaka-Douzono
S
S
Suzu
M
M
Yamada
E
E
Misawa
N
N
Wakimoto
S
S
Shimamura
K
K
Hatake
K
K
Motoyoshi
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D003114:Colony-Forming Units Assay; D003520:Cyclophosphamide / Q000494:pharmacology; D003561:Cytarabine / Q000494:pharmacology; D004351:Drug Resistance; D005472:Fluorouracil / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D017493:Leukocyte Common Antigens / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D016177:Macrophage-1 Antigen / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017154:Stromal Cells / Q000166:cytology* / Q000187:drug effects* / Q000276:immunology
D000970:Antineoplastic Agents; D016177:Macrophage-1 Antigen; D003561:Cytarabine; D016173:Macrophage Colony-Stimulating Factor; D003520:Cyclophosphamide; D017493:Leukocyte Common Antigens; D005472:Fluorouracil