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KMID : 1377020190160010059
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Tissue Engineering and Regenerative Medicine
2019 Volume.16 No. 1 p.59 ~ p.68
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GM-CSF Enhances Mobilization of Bone Marrow Mesenchymal Stem Cells via a CXCR4-Medicated Mechanism
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Kim Ji-Young
Kim Na-Kyeong
Park So-Ra
Choi Byung-Hyune
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Abstract
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Background: This study was conducted to investigate the effect of granulocyte?macrophage colony-stimulating factor (GM-CSF) on the mobilization of mesenchymal stem cells (MSCs) from the bone marrow (BM) into the peripheral blood (PB) in rats.
Methods: GM-CSF was administered subcutaneously to rats at 50 μg/kg body weight for 5 consecutive days. The BM and PB of rats were collected at 1, 3, and 5 days during the administration for analysis.
Results: Upon GM-CSF administration, the number of mononuclear cells increased rapidly at day 1 both in the BM and PB. This number decreased gradually over time in the BM to below the initial amount by day 5, but was maintained at a high level in the PB until day 5. The colony-forming unit?fibroblasts were increased in the PB by 10.3-fold at day 5 of GM-CSF administration, but decreased in the BM. Compared to GM-CSF, granulocyte-colony stimulating factor (G-CSF) stimulated lower levels of MSC mobilization from the BM to the PB. Immunohistochemical analysis revealed that GM-CSF induced a hypoxic and proteolytic microenvironment and increased C-X-C chemokine receptor type 4 (CXCR4) expression in the BM. GM-CSF added to BM MSCs in vitro dose-dependently increased CXCR4 expression and cell migration. G-CSF and stromal cell derived factor-1 (SDF-1) showed similar results in these in vitro assays. Know-down of CXCR4 expression with siRNA significantly abolished GM-CSF- and G-CSF-induced MSC migration in vitro, indicating the involvement of the SDF-1?CXCR4 interaction in the mechanism.
Conclusion: These results suggest that GM-CSF is a useful tool for mobilizing BM MSCs into the PB.
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KEYWORD
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Granulocyte?macrophage colony-stimulating factor, Mesenchymal stem cells, Bone marrow, Mobilization, Hypoxia
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