GM-CSF Enhances Mobilization of Bone Marrow Mesenchymal Stem Cells via a CXCR4-Medicated Mechanism
10.1007/s13770-018-0163-5
- Author:
Jiyoung KIM
1
;
Na Kyeong KIM
;
So Ra PARK
;
Byung Hyune CHOI
Author Information
1. Department of Physiology and Biophysics, Inha University College of Medicine, 100 Inha-ro Nam-gu, Incheon 22212, Korea. srpark@inha.ac.kr bryan@inha.ac.kr
- Publication Type:Original Article
- Keywords:
Granulocyte-macrophage colony-stimulating factor;
Mesenchymal stem cells;
Bone marrow;
Mobilization;
Hypoxia
- MeSH:
Animals;
Anoxia;
Body Weight;
Bone Marrow;
Cell Movement;
Granulocyte Colony-Stimulating Factor;
Granulocyte-Macrophage Colony-Stimulating Factor;
In Vitro Techniques;
Mesenchymal Stromal Cells;
Rats;
RNA, Small Interfering;
Stromal Cells
- From:
Tissue Engineering and Regenerative Medicine
2019;16(1):59-68
- CountryRepublic of Korea
- Language:English
-
Abstract:
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.
