Grant: Operating Grant

Heart disease and dysfunction can lead to the death of heart muscle cells, termed cardiomyocytes, resulting in the loss of cardiac muscle function. A method to replace damaged muscle cells using cell therapy would be greatly beneficial for the restoration of heart muscle function. Human embryonic stem (ES) cells have shown some promise as a source of cardiomyocytes for cell therapy. One drawback of ES cell work is that these cells can form any cell type in the body. Thus directing the differentiation into one cell type has been a challenge. While protocols have been developed to induce ES cell differentiation into cultures containing 40-80% cardiomyocytes, the procedure is variable and the cardiomyocytes are a mixture of working myocardium (from the atrial or ventricles) and pacemaker cells (from the conduction system that generate the heart beat). To increase our ability of using ES cells for cell therapy, a detailed understanding is required of the molecular pathways that drive an embryonic stem cell to differentiate and mature into cardiac muscle. The overall goal of this grant is to enhance our understanding of the molecular events that regulate cardiomyogenesis with an ultimate goal of using this knowledge to develop cell therapy methods to repair damaged heart muscle.