Cardiac mesenchymal stem cells contribute to scar formation after myocardial infarction

Cardiovasc Res. 2011 Jul 1;91(1):99-107. doi: 10.1093/cvr/cvr061. Epub 2011 Feb 28.


Aims: Therapeutic advances in prevention and treatment of myocardial infarction (MI) have decreased patient mortality and increased concern about efficient repair and scar formation, processes that are necessary to attenuate complications such as adverse remodelling and heart failure. Since the rapid accumulation and activity of cardiac fibroblasts is critical for proper scar formation, we hypothesized that infarct fibroblasts are generated by a cardiac-resident progenitor cell population.

Methods and results: We found that infarct fibroblasts in C57BL/6 mice are generated by a mesenchymal stem cell (MSC) population that responds robustly to injury by proliferating and accumulating in the infarct. We report that stem cell-derived fibroblasts contribute to the formation of a scar after an infarction by differentiating into matrix-producing fibroblasts closely associated with fibrillar collagen in the infarct. Further characterization of these cells revealed a heterogenous population with expression of both stem cell and canonical cardiac fibroblast markers, suggesting that some have a commitment to the fibroblast phenotype. Our in vitro study of these cells shows that they have extended self-renewal capability and express the primitive marker Nanog. In keeping with these observations, we also report that these cells are multipotent and differentiate readily into fibroblasts as well as other mesenchymal lineages.

Conclusion: Cells with the properties of MSCs participate in wound healing after MI in the adult heart.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Analysis of Variance
  • Animals
  • Biomarkers / metabolism
  • Cell Differentiation
  • Cell Lineage
  • Cell Proliferation
  • Cells, Cultured
  • Cicatrix / metabolism
  • Cicatrix / pathology*
  • Disease Models, Animal
  • Fibrillar Collagens / metabolism
  • Fibroblasts / metabolism
  • Fibroblasts / pathology*
  • Homeodomain Proteins / metabolism
  • Hyaluronan Receptors / metabolism
  • Male
  • Mesenchymal Stem Cells / metabolism
  • Mesenchymal Stem Cells / pathology*
  • Mice
  • Mice, Inbred C57BL
  • Multipotent Stem Cells / metabolism
  • Multipotent Stem Cells / pathology*
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / pathology*
  • Myocardium / metabolism
  • Myocardium / pathology*
  • Myofibroblasts / metabolism
  • Myofibroblasts / pathology
  • Nanog Homeobox Protein
  • Phenotype
  • Time Factors
  • Wound Healing


  • Biomarkers
  • Cd44 protein, mouse
  • Fibrillar Collagens
  • Homeodomain Proteins
  • Hyaluronan Receptors
  • Nanog Homeobox Protein
  • Nanog protein, mouse