Soluble c-kit receptor mobilizes hematopoietic stem cells to peripheral blood in mice.
OBJECTIVE
The mechanisms of mobilization of hematopoietic stem cells (HSC) from bone marrow to peripheral blood (PB) by cytokines are poorly understood. One hypothesis is that cytokines disrupt cytoadhesive interactions of stem cells with bone marrow stroma. The soluble portion of c-kit (s-kit) binds stem cell factor (SCF) and can specifically block the ability of SCF to bind HSC.


METHODS
To examine stem cell mobilization by s-kit, we prepared PB mononuclear cells from s-kit- or granulocyte colony-stimulating factor (G-CSF)-treated mice and assayed their colony-forming abilities and their long-term reconstituting abilities by transplantation into lethally irradiated Ly-5.2 congenic mice.


RESULTS
We confirmed the published findings that human recombinant s-kit can block SCF-stimulated hematopoietic colony growing. We then found that s-kit could mobilize colony-forming cells from bone marrow to PB, and we found long-term reconstitution cells in the PB from s-kit-treated mice. The majority of s-kit-mobilized stem cells were in the CD34(+) cell population. We also tested the additive effect between G-CSF and s-kit. The mean percentages of donor cells in the mice transplanted with Lin(-) cells from the G-CSF-treated mice and the G-CSF/s-kit-treated mice were 44.6% and 64.8%, respectively (p=0.028).


CONCLUSIONS
These findings demonstrate that stem cells with long-term engraftment capabilities can be mobilized by s-kit, and that s-kit combined with G-CSF treatment leads to significant enhancement of engraftment efficiency, suggesting mobilization via disruption between c-kit and SCF as the mechanism.
Nakamura
Yuki
Y
Second Department of Internal Medicine, Faculty of Medicine, Tottori University, Yonago, Japan.
Tajima
Fumihito
F
Ishiga
Kiyomi
K
Yamazaki
Hidetoshi
H
Oshimura
Mitsuo
M
Shiota
Goshi
G
Murawaki
Yoshikazu
Y
D000818:Animals; D018952:Antigens, CD34 / Q000032:analysis; D002469:Cell Separation; D004353:Drug Evaluation, Preclinical; D004357:Drug Synergism; D006085:Graft Survival; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D000078224:Lenograstim; D051379:Mice; D008810:Mice, Inbred C57BL; D036102:Peripheral Blood Stem Cell Transplantation; D019009:Proto-Oncogene Proteins c-kit / Q000494:pharmacology*; D011828:Radiation Chimera; D011994:Recombinant Proteins / Q000494:pharmacology; D019089:Stem Cell Factor / Q000494:pharmacology
D018952:Antigens, CD34; D007377:Interleukin-3; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D016179:Granulocyte Colony-Stimulating Factor; D000078224:Lenograstim; D019009:Proto-Oncogene Proteins c-kit