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Tissue-Specific Stem Cells
Article first published online: 9 JUL 2009
Copyright © 2009 AlphaMed Press
Volume 27, Issue 11, pages 2734–2743, November 2009
How to Cite
Mias, C., Lairez, O., Trouche, E., Roncalli, J., Calise, D., Seguelas, M.-H., Ordener, C., Piercecchi-Marti, M.-D., Auge, N., Salvayre, A. N., Bourin, P., Parini, A. and Cussac, D. (2009), Mesenchymal Stem Cells Promote Matrix Metalloproteinase Secretion by Cardiac Fibroblasts and Reduce Cardiac Ventricular Fibrosis After Myocardial Infarction. STEM CELLS, 27: 2734–2743. doi: 10.1002/stem.169
Author contributions: C.M.: Conception and design, collection and/or assembly of data, data analysis and interpretation, manuscript writing; O.L.: Collection and/or assembly of data, data analysis and interpretation; E.T.: Collection and/or assembly of data, data analysis and interpretation; J.R.: Conception and design; D. Calise: Collection and/or assembly of data, data analysis and interpretation; M.-H.S.: Collection and/or assembly of data; C.O.: Collection and/or assembly of data; M.-D.P.-M.: Collection and/or assembly of data; N.A.: Collection and/or assembly of data; A.N.S.: Collection and/or assembly of data; P.B.: Conception and design, provision of study material or patients; A.P.: Conception and design, data analysis and interpretation, manuscript writing, final approval of manuscript, financial support; D. Cussac: Conception and design, data analysis and interpretation, manuscript writing, final approval of manuscript.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLS EXPRESS 2009.
- Issue published online: 6 NOV 2009
- Article first published online: 9 JUL 2009
- Accepted manuscript online: 9 JUL 2009 12:00AM EST
- Manuscript Accepted: 28 JUN 2009
- Manuscript Received: 9 MAR 2009
- National Research Agency (ANR) (Grant under program Physiopathologie des Maladies Humaines, project SYNMESCARI)
- Région Midi-Pyrénées
- Fondation pour la Recherche Médicale (FRM)
- Mesenchymal stem cells;
- Cardiac fibroblasts;
- Matrix metalloproteinases;
- Myocardial infarction;
- Therapeutic efficacy
Recent studies showed that mesenchymal stem cells (MSCs) transplantation significantly decreased cardiac fibrosis; however, the mechanisms involved in these effects are still poorly understood. In this work, we investigated whether the antifibrotic properties of MSCs involve the regulation of matrix metalloproteinases (MMPs) and matrix metalloproteinase endogenous inhibitor (TIMP) production by cardiac fibroblasts. In vitro experiments showed that conditioned medium from MSCs decreased viability, α-smooth muscle actin expression, and collagen secretion of cardiac fibroblasts. These effects were concomitant with the stimulation of MMP-2/MMP-9 activities and membrane type 1 MMP expression. Experiments performed with fibroblasts from MMP2-knockout mice demonstrated that MMP-2 plays a preponderant role in preventing collagen accumulation upon incubation with conditioned medium from MSCs. We found that MSC-conditioned medium also decreased the expression of TIMP2 in cardiac fibroblasts. In vivo studies showed that intracardiac injection of MSCs in a rat model of postischemic heart failure induced a significant decrease in ventricular fibrosis. This effect was associated with the improvement of morphological and functional cardiac parameters. In conclusion, we showed that MSCs modulate the phenotype of cardiac fibroblasts and their ability to degrade extracellular matrix. These properties of MSCs open new perspectives for understanding the mechanisms of action of MSCs and anticipate their potential therapeutic or side effects. STEM CELLS 2009;27:2734–2743