Following transmural myocardial infarction left ventricular remodeling (LVR) with chamber dilation and hypertrophy occurs to compensate for loss of contracting myocardium. Although stable LV remodeling may be achieved for a period of time, progressive myocardial dysfunction can develop and ultimately lead to overt congestive heart failure (CHF). The currently available therapeutic options for heart failure due to transmural left ventricular infarct are limited. Several exciting recent studies have shown that tissue specific stem cells may have the ability to generate cells of tissues from unrelated organs. We have identified a population of primitive cells in normal human post-natal bone marrow that have multipotent differentiation and extensive proliferation potential, which we have named Multipotent Adult Progenitor Cells or MAPC. The proposed research will examine the ability of a novel fibrin patch to deliver allogenic or autologous cells into myocardial infarcts to improve LV function, and to prevent the transition to heart failure. Using a swine model of postinfarction LV remodeling, the effect of cell transplantation on LV contractile function and myocardial energy metabolism will be examined using MRI and 31P-MR spectroscopy, respectively. The following hypothesis will be tested: 1) A fibrin-stem cell patch can deliver a high concentration of allogenic MAPC onto the surface of ischemic myocardium. In response to myocardial ischemic signals, the stem cells will leave the fibrin patch and home to the ischemic myocardium to repair the infarct region and to prevent the formation of LV aneurysm. 2) A fibrin-thrombin patch can be used to deliver a high concentration of autologous bone marrow stem cells within 30 minutes. The autologous bone marrow cells will gradually leave the patch and migrate to the infarct area where they continue to divide and differentiate into myocytes, smooth muscle cells and endothelial cells, and replace the myocardial infarct. 3) An artificial myocardium generated by entrapping MAPC in a bipolymer fibrin gel and allowing the cells to partially differentiate and develop contractile function in vitro before implantation onto the infarct region will reestablish LV contractile function. By providing insight into the effects of the cellular patch transplantation, the results may lead to better preventive, diagnostic and therapeutic modalities for LV injury.
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