GM-CSF Enhances Mobilization of Bone Marrow Mesenchymal Stem Cells via a CXCR4-Medicated Mechanism
Tissue Engineering and Regenerative Medicine
;
(6): 59-68, 2019.
Article
in English
| WPRIM
| ID: wpr-742384
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Body Weight
/
Bone Marrow
/
In Vitro Techniques
/
Cell Movement
/
Granulocyte Colony-Stimulating Factor
/
Granulocyte-Macrophage Colony-Stimulating Factor
/
Stromal Cells
/
RNA, Small Interfering
/
Mesenchymal Stem Cells
/
Hypoxia
Limits:
Animals
Language:
English
Journal:
Tissue Engineering and Regenerative Medicine
Year:
2019
Type:
Article
Similar
MEDLINE
...
LILACS
LIS