Intracardiac fibroblasts, but not bone marrow derived cells, are the origin of myofibroblasts.pdf

Cardiovascular PathologyOriginal Article Intracardiac fibroblasts, but not bone marrow derived cells, are the origin of myofibroblasts in myocardial infarct repair Toshiyuki Yanoa, Tetsuji Miuraa,T, Yoshihiro Ikedaa, Eiji Matsudab, Keiji Saitob, Takayuki Mikia, Hironori Kobayashia, Yasuhiro Nishinoa, Seiji Ohtanic, Kazuaki Shimamotoa aSecond Department of Internal Medicine, Sapporo Medical University, School of Medicine, Sapporo 060-8543, Japan bProduct Research Department, Chugai Pharmaceutical Co., Ltd., Shizuoka, Japan cDepartment of Bioengineering, Sapporo Medical University, School of Medicine, Sapporo 060-8543, Japan Received 9 December 2004; received in revised form 21 April 2005; accepted 17 May 2005 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 w