Although cell transplant therapy has shown some promise in restoring tissue mass and improving left ventricular function after experimental myocardial infarction, the two major obstacles that must be overcome are 1) having an available and reliable source of cells, and 2) being able to administer the cells in a non-invasive fashion, especially in those patients who are at high risk for cardiac surgery. In this protocol we are proposing to use a commercial source of allogeneic rat mesenchymal stem cells (MSC). The ability to use allogeneic MSC to engraft infarcts early after coronary artery occlusion may constitute a significant therapeutic strategy, since the mesenchymal stem cells do not cause an immunologic response. The rat mesenchymal stem cells can be injected directly into the infarct or, in a non-invasive mode, administered intravenously. Preliminary studies have shown that when they are injected intravenously these cells """"""""home"""""""" to areas of inflammation. The advantages of intravenous administration of cells as a clinical approach includes the ability to give one or repeated injections without the need for thoracotomy. However, the outcome of this approach on left ventricular function and healing (remodeling of the heart) is unknown. Therefore we propose to study mesenchymal stem cell implantation in a rat experimental myocardial infarct model. We will test both direct injection and intravenous injection in reperfused and non-reperfused infarcts. We will also determine whether there are differences in survival of the cells and their effects on LV function depending on the time of cell administration (early-within two hours of coronary artery occlusion, or late- four days after coronary artery occlusion). Immunohistochemistry of cells within the scar will include analysis for the Y chromosome (evidence of successful transplantation), cardiac troponin T, alpha actinin, tropomyosin, myosin heavy chain alpha and phospholamban, which will confirm that transplanted stem cells survived and either developed or did not develop a cardiac cell phenotype. The overall endpoints of this study will be to determine whether MSC therapy will enhance left ventricular function and reduce left ventricular dilation and remodeling after myocardial infarction, especially when commercially available cells are administered intravenously.
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