Bone marrow-derived myofibroblasts contribute functionally to scar formation after myocardial infarction

J Pathol. 2008 Feb;214(3):377-86. doi: 10.1002/path.2281.

Abstract

Myofibroblasts play a major role in scar formation during wound healing after myocardial infarction (MI). Their origin has been thought to be interstitial cardiac fibroblasts. However, the bone marrow (BM) can be a source of myofibroblasts in a number of organs after injury. We have studied the temporal, quantitative and functional role of BM-derived (BMD) myofibroblasts in myocardial scar formation. MI was induced by permanent coronary artery ligation in mice reconstituted with EGFP or pro-Col1A2 transgenic BM. In the latter, luciferase and beta-galactosidase transgene expression mirrors that of the endogenous pro-collagen 1A2 gene, which allows for functional assessment of the recruited cells. After MI, alpha-SMA-positive myofibroblasts and collagen I gradually increased in the infarct area until day 14 and remained constant afterwards. Numerous EGFP-positive BMD cells were present during the first week post-MI, and gradually decreased afterwards until day 28. Peak numbers of BMD myofibroblasts, co-expressing EGFP and alpha-SMA, were found on day 7 post-MI. An average of 21% of the BMD cells in the infarct area were myofibroblasts. These cells constituted up to 24% of all myofibroblasts present. By in vivo IVIS imaging, BMD myofibroblasts were found to be active for collagen I production and their presence was confined to the infarct area. These results show that BMD myofibroblasts participate actively in scar formation after MI.

Publication types

  • Comparative Study

MeSH terms

  • Actins / analysis
  • Actins / genetics
  • Animals
  • Bone Marrow Cells / pathology*
  • Cicatrix / enzymology
  • Cicatrix / pathology*
  • Collagen / genetics
  • Collagen / metabolism
  • Collagen Type I
  • Fibroblasts / pathology
  • Gene Expression
  • Green Fluorescent Proteins / analysis
  • Green Fluorescent Proteins / genetics
  • Immunohistochemistry
  • Ligation
  • Luciferases / analysis
  • Luciferases / genetics
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Models, Animal
  • Myocardial Infarction / enzymology
  • Myocardial Infarction / pathology*
  • Myocardium / enzymology
  • Myocardium / pathology*
  • Wound Healing*
  • beta-Galactosidase / analysis
  • beta-Galactosidase / genetics

Substances

  • Actins
  • Collagen Type I
  • Green Fluorescent Proteins
  • Collagen
  • Luciferases
  • beta-Galactosidase