Phenotypic modulation and turnover of bone marrow-derived cells after myocardial infarction in rats

Background: Bone marrow-derived cells (BMCs) are critically involved in inflammation and regeneration after myocardial infarction (MI). However, the participation of BMCs in the reconstruction of infarcted myocardium remains unclear. In this study, we investigated phenotypic modulation of BMCs and their turnover in the heart following MI. Methods and results: MI was produced in rats with intra-bone marrow-bone marrow transplantation from the syngenic rats expressing green fluorescence protein (GFP). The number of GFP-positive BMCs recruited to the infarcted myocardium peaked at 3 days after MI, and the majority of BMCs recruited to the heart after MI underwent turnover within 2 weeks. This turnover rate was unchanged for up to 16 weeks after MI, although the number of BMCs recruited to the infarcted myocardium rapidly decreased between 2 and 8 weeks after MI. A small number of BMCs recruited to the heart were positive for CD31 and alpha-smooth muscle actin, and the majority of these were positive for Vimentin at 3 days and 4 weeks after MI. None of BMCs expressed alpha-actinin or von Willebrand factor 4 weeks after MI. Conclusions: These results suggest that BMCs recruited to the heart underwent phenotypic modulation to a fibroblastic cell type and turnover within 2 weeks after MI without differentiating into cardiomyocytes or endothelial cells, and that although the number of BMCs in the infarcted myocardium decreased over time, the rate of turnover remained relatively constant during the chronic phase of MI. (C) 2011 Elsevier Inc. All rights reserved.