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

Journal article

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.

Authors: van Amerongen, M; Bou-Gharios, G; Popa, E; van Ark, J; Petersen, A

• Publication status: Published
• Journal: Journal of pathology
• Volume: 214
• Issue: 3
• Pages: 377-386
• Publication date: 2008-02-01
• DOI: 10.1002/path.2281
• EISSN: 1096-9896
• ISSN: 0022-3417
• Language: English
• Keywords: Animals; Green Fluorescent Proteins; Luciferases; Bone Marrow Cells; Immunohistochemistry; Collagen Type I; Collagen; Myocardium; Mice, Inbred C57BL; beta-Galactosidase; Mice, Transgenic; Fibroblasts; Cicatrix; Mice; Male; Gene Expression; Actins; Models, Animal; Ligation; Myocardial Infarction; Wound Healing