GM-CSF Enhances Mobilization of Bone Marrow Mesenchymal Stem Cells via a CXCR4-Medicated Mechanism
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.
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.
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.
These results suggest that GM-CSF is a useful tool for mobilizing BM MSCs into the PB.
KeywordsGranulocyte–macrophage colony-stimulating factor Mesenchymal stem cells Bone marrow Mobilization Hypoxia
This research was supported by a Grant of the Korea Health Technology R&D Project funded by the Ministry of Health and Welfare, Republic of Korea (HI17C2191).
Compliance with ethical standards
Conflict of interest
The authors have no potential conflicts of interest.
All animal procedures were approved by the committee of Institutional Animal Care (INHA-IACUC Approval Number: INHA 130625-217-1).
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