Summary |
Cardiovascular disease is one of the major causes of death among the adult population in the United States. The limited availability of donor hearts has encouraged the investigation of stem cells as a possible therapeutic approach to cardiomyocyte damage caused by myocardial infarction (MI). Human mesenchymal stem cells (hMSCs) have been the most studied cell population because of their capacity to easily expand in culture, myogenetic capabilities, and their autologous nature with potential therapeutic use. The microenvironment of transplanted stem cells plays a crucial role in the efficiency of stem cell engraftment and differentiation, with successful transplantation often limited by low cell survival rates. Research suggests that the protein thymosin beta-4 (T(34) promotes cardiac cell survival and demonstrates a cardioprotective role in injured myocardium. Therefore, we sought to evaluate the role of Tp4 on hMSC engraftment, survival, and differentiation in murine myocardium. Female hMSCs transfected with a mitochondrial red fluorescent protein (dsRed hMSCs) were obtained from the Tulane Center for Gene Therapy. Tp4-treated and nontreated dsRed hMSCs were injected into the anterior surface of the left ventricle of nude mice that either received or did not receive a systemic Tp4 treatment. Fluorescence microscopy was used to locate the injected cells in paraffin embedded sections of the heart at 1 and 4 week time points. Serial seetions were used to determine differentiation of these hMSCs into cardiomyocytes, vascular smooth muscle cells, and endothelial cells. Preliminary data from this study suggests that Tp4 can increase hMSC engraftment. survival, and differentiation in murine myocardium. Conditioning the cells and/or tissue may help to enhance cell engraftment and survival, and promote differentiation, providing a more suitable microenvironment for transplantation. It is anticipated that this approach will contribute to the study of cell transplantation therapies for cardiovascular disease. |