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Publication : Defining the role of mesenchymal stromal cells on the regulation of matrix metalloproteinases in skeletal muscle cells.

First Author  Sassoli C Year  2014
Journal  Exp Cell Res Volume  323
Issue  2 Pages  297-313
PubMed ID  24631289 Mgi Jnum  J:216264
Mgi Id  MGI:5608571 Doi  10.1016/j.yexcr.2014.03.003
Citation  Sassoli C, et al. (2014) Defining the role of mesenchymal stromal cells on the regulation of matrix metalloproteinases in skeletal muscle cells. Exp Cell Res 323(2):297-313
abstractText  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 alpha-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.
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