Cardiac mesenchymal stem cells contribute to scar formation after myocardial infarction

Signe Carlson, Joann Trial, Christian Soeller, Mark L. Entman

Research output: Contribution to journalArticlepeer-review

85 Scopus citations

Abstract

AimsTherapeutic 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 resultsWe 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.ConclusionCells with the properties of MSCs participate in wound healing after MI in the adult heart.

Original languageEnglish (US)
Pages (from-to)99-107
Number of pages9
JournalCardiovascular Research
Volume91
Issue number1
DOIs
StatePublished - Jul 1 2011

Keywords

  • Fibroblast precursors
  • Infarct repair
  • Mesenchymal stem cells
  • Precursor cell differentiation

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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