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

• Published in: Experimental cell research Vol. 323; no. 2; pp. 297 - 313
• Main Authors: Sassoli, Chiara, Nosi, Daniele, Tani, Alessia, Chellini, Flaminia, Mazzanti, Benedetta, Quercioli, Franco, Zecchi-Orlandini, Sandra, Formigli, Lucia
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.05.2014; Elsevier BV
• Subjects: 60 APPLIED LIFE SCIENCES; ACTIN; Actins - genetics; Actins - metabolism; ANIMAL TISSUES; Animals; Cell Differentiation; Cell Movement; Cells, Cultured; Cellular biology; COLLAGEN; Collagen Type I - genetics; Collagen Type I - metabolism; Culture Media, Conditioned - pharmacology; Cytokines; Cytokines - pharmacology; EDTA; FIBROBLASTS; Fibroblasts - cytology; Fibroblasts - drug effects; Fibroblasts - metabolism; FLUORESCENCE; Heterocyclic Compounds, 1-Ring - pharmacology; Humans; Intercellular Signaling Peptides and Proteins - pharmacology; LYMPHOKINES; Matrix Metalloproteinase 2 - genetics; Matrix Metalloproteinase 2 - metabolism; Matrix Metalloproteinase 9 - genetics; Matrix Metalloproteinase 9 - metabolism; Matrix Metalloproteinase Inhibitors - pharmacology; Matrix metalloproteinases (MMPs); Mesenchymal stromal cells (MSCs); Mesenchymal Stromal Cells - metabolism; Mice; Muscle Fibers, Skeletal - drug effects; Muscle Fibers, Skeletal - metabolism; MUSCLES; Musculoskeletal system; Myoblast differentiation; NIH 3T3 Cells; ORGANIC FLUORINE COMPOUNDS; Proteins; Satellite cells; Skeletal fibroblasts; Stem cells; Sulfones - pharmacology; Tissue Inhibitor of Metalloproteinase-1 - genetics; Tissue Inhibitor of Metalloproteinase-1 - metabolism; Tissue Inhibitor of Metalloproteinase-2 - genetics; Tissue Inhibitor of Metalloproteinase-2 - metabolism; RT; TIMP-2; TIMP-1; DM; PFA; Satellite cells; EDL; MSC-CM; GFP; MSCs; Myoblast differentiation; Matrix metalloproteinases (MMPs); TGF-β; Skeletal fibroblasts; DIC; PBS; SDS; Pax-7; IL-1; HGF; VEGF; MMPs; EDTA; PVDF; ROI; bFGF; ECM; α-sma; Mesenchymal stromal cells (MSCs); PMSF
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1016/j.yexcr.2014.03.003

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. •MSC-CM contains paracrine factors that up-regulate MMP expression and function in different skeletal muscle cells.•MSC-CM promotes myoblast and satellite cell migration, proliferation and differentiation.•MSC-CM negatively interferes with fibroblast-myoblast transition in primary skeletal fibroblasts.•Paracrine factors from MSCs modulate the fibrotic response and improve the endogenous mechanisms of muscle regeneration.