Intracardiac fibroblasts, but not bone marrow derived cells, are the origin of myofibroblasts in myocardial infarct repair

Abstract

Summary Origin of myofibroblasts in infarcted myocardium was examined by using rats in which bone marrow of green fluorescent protein (GFP)-transgenic mice had been transplanted. GFP was not detected in myofibroblasts at either 3 or 7 days after infarction, suggesting that proliferating myofibroblasts in infarcted myocardium are derived from resident fibroblasts rather than circulating precursor cells of bone marrow origin. Background Myofibroblasts play important roles in the repair process of myocardial infarct, and their origin has been assumed to be interstitial fibroblasts in the heart. However, bone marrow-derived myofibroblasts have recently been identified in pathological fibrosis in extracardiac tissues. In this study, we aimed to determine whether some of the myofibroblasts in infarcted myocardium are derived from circulating precursor cells of bone marrow origin. Methods and Results Bone marrow (BM) of GFP-transgenic mice was transplanted into nude rats, and their coronary arteries were occluded for 60 min and reperfused for 3 or 7 days. Non-BM-transplanted rats served as controls. At 3 days after infarction, some endothelial cells were GFP-positive, indicating that they were of bone marrow origin. Predominant cells in infarcted regions were macrophages and neutrophils, and there were only a small number of vimentin-positive cells and fewer myofibroblasts, both of which were GFP-negative. At 7 days after infarction, there were numerous myofibroblasts in granulation tissue replacing necrotic myocytes, and none of them showed GFP signals, whereas some cells were positive for both GFP and vimentin. Appearance of myofibroblasts and extent of the infarct repair in BM-transplanted and those in non-transplanted rats were similar. Conclusions The findings in this study suggest that proliferating myofibroblasts in infarcted myocardium are derived from resident fibroblasts rather than circulating precursor cells of bone marrow origin.