title: Bone marrow-derived myofibroblasts contribute functionally to scar formation after myocardial infarction.
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.
authors: Department of Pathology and Laboratory Medicine, University Medical Center Groningen, University of Groningen, The Netherlands. machteld.van-amerongen@mpi-bn.mpg.de
authors: M J
authors: MJ
authors: van Amerongen
authors: G
authors: G
authors: Bou-Gharios
authors: Er
authors: E
authors: Popa
authors: J
authors: J
authors: van Ark
authors: A H
authors: AH
authors: Petersen
authors: G M
authors: GM
authors: van Dam
authors: M J A
authors: MJ
authors: van Luyn
authors: M C
authors: MC
authors: Harmsen
mesh_terms: D000199:Actins / Q000032:analysis / Q000235:genetics; D000818:Animals; D001854:Bone Marrow Cells / Q000473:pathology*; D002921:Cicatrix / Q000201:enzymology / Q000473:pathology*; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D024042:Collagen Type I; D005347:Fibroblasts / Q000473:pathology; D015870:Gene Expression; D049452:Green Fluorescent Proteins / Q000032:analysis / Q000235:genetics; D007150:Immunohistochemistry; D008026:Ligation; D008156:Luciferases / Q000032:analysis / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D023421:Models, Animal; D009203:Myocardial Infarction / Q000201:enzymology / Q000473:pathology*; D009206:Myocardium / Q000201:enzymology / Q000473:pathology*; D014945:Wound Healing; D001616:beta-Galactosidase / Q000032:analysis / Q000235:genetics
chemical_list: D000199:Actins; D024042:Collagen Type I; D049452:Green Fluorescent Proteins; D003094:Collagen; D008156:Luciferases; D001616:beta-Galactosidase