Temporal changes in stem cells in the circulation and myocardium of mice with Coxsackie virus B3-induced myocarditis

Our goal was to investigate temporal changes in stem cell in the circulation and myocardium of mice with Coxsackie virus B3-induced myocarditis. Groups of mice were administered Eagle's minimal essential medium or virus solution. The animals were further divided into six subgroups based on the following time points post-inoculation: 1, 3, 7, 14, 21, and 28 days. Ten animals were studied in each subgroup. Circulating blood mononuclear cells were collected from the heart and analyzed using flow cytometry. Myocardial inflammation, stem cell expression, and cell proliferation were detected by histology and immunofluorescence. H&E staining revealed neutrophil infiltration and bleeding by day 3 post-infection. Myeloperoxidase and reactive oxygen species levels peaked by day 3 and were followed by myocyte loss and collagen deposition. Circulating mesenchymal stem cells also peaked by day 3. In contrast, hematopoietic stem cells remained sustained increase within day 14. Immunohistochemical microscopy also showed a marked increase in cardiac stem cells by day 14. The kinetics of this increase was consistent with a rise in proliferating cells expressing nuclear and cytoplasmic proteins that are typical of cardiomyocyte or vascular endothelial cells. These results demonstrate the rapid kinetics of progenitor cells during viral myocarditis and suggest that the optimal time to administer cell therapy to induce heart repair is within 2 weeks after viral infection. (c) 2007 Elsevier Inc. All rights reserved.