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Defining the role of mesenchymal stromal cells on the regulation of matrix metalloproteinases in skeletal muscle cells
- Source :
- Experimental Cell Research. 323(2):297-313
- Publication Year :
- 2014
- Publisher :
- Elsevier BV, 2014.
-
Abstract
- Recent studies indicate that mesenchymal stromal cell (MSC) transplantation improves healing of injured and diseased skeletal muscle, although the mechanisms of benefit are poorly understood. In the present study, we investigated whether MSCs and/or their trophic factors were able to regulate matrix metalloproteinase (MMP) expression and activity in different cells of the muscle tissue. MSCs in co-culture with C2C12 cells or their conditioned medium (MSC-CM) up-regulated MMP-2 and MMP-9 expression and function in the myoblastic cells; these effects were concomitant with the down-regulation of the tissue inhibitor of metalloproteinases (TIMP)-1 and -2 and with increased cell motility. In the single muscle fiber experiments, MSC-CM administration increased MMP-2/9 expression in Pax-7+ satellite cells and stimulated their mobilization, differentiation and fusion. The anti-fibrotic properties of MSC-CM involved also the regulation of MMPs by skeletal fibroblasts and the inhibition of their differentiation into myofibroblasts. The treatment with SB-3CT, a potent MMP inhibitor, prevented in these cells, the decrease of α-smooth actin and type-I collagen expression induced by MSC-CM, suggesting that MSC-CM could attenuate the fibrogenic response through mechanisms mediated by MMPs. Our results indicate that growth factors and cytokines released by these cells may modulate the fibrotic response and improve the endogenous mechanisms of muscle repair/regeneration.
- Subjects :
- Stromal cell
Mesenchymal stromal cells (MSCs)
Muscle Fibers, Skeletal
Matrix metalloproteinase
Biology
Matrix Metalloproteinase Inhibitors
Collagen Type I
Heterocyclic Compounds, 1-Ring
Mice
Cell Movement
Satellite cells
Matrix metalloproteinases (MMPs)
medicine
Animals
Humans
Sulfones
Actin
Cells, Cultured
Tissue Inhibitor of Metalloproteinase-2
Tissue Inhibitor of Metalloproteinase-1
Mesenchymal stem cell
Lymphokine
Skeletal muscle
Cell Differentiation
Mesenchymal Stem Cells
Cell Biology
Fibroblasts
Actins
Cell biology
medicine.anatomical_structure
Matrix Metalloproteinase 9
Myoblast differentiation
Culture Media, Conditioned
Immunology
NIH 3T3 Cells
Cytokines
Intercellular Signaling Peptides and Proteins
Matrix Metalloproteinase 2
matrix metalloproteinases
mesenchymal stromal cells
myoblast differentiation
satellite cells
skeletal fibroblasts
C2C12
Myofibroblast
Skeletal fibroblasts
Subjects
Details
- ISSN :
- 00144827
- Volume :
- 323
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Experimental Cell Research
- Accession number :
- edsair.doi.dedup.....3a10231755170efedacc6f8271ffccb1
- Full Text :
- https://doi.org/10.1016/j.yexcr.2014.03.003