Tissue Eng Regen Med.  2019 Feb;16(1):59-68. 10.1007/s13770-018-0163-5.

GM-CSF Enhances Mobilization of Bone Marrow Mesenchymal Stem Cells via a CXCR4-Medicated Mechanism

Affiliations
  • 1Department 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
  • 2Department of Biomedical Sciences, Inha University College of Medicine, 100 Inha-ro Nam-gu, Incheon 22212, Korea. srpark@inha.ac.kr bryan@inha.ac.kr

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.

Keyword

Granulocyte-macrophage colony-stimulating factor; Mesenchymal stem cells; Bone marrow; Mobilization; Hypoxia

MeSH Terms

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
Granulocyte Colony-Stimulating Factor
Granulocyte-Macrophage Colony-Stimulating Factor
RNA, Small Interfering
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