Coronary heart disease is one of the leading causes of death in humans. Coronary arteries are blood vessels that supply the heart muscle with blood and oxygen. Thus, blockage of a coronary artery deprives the heart muscle of blood and oxygen, causing injury to the heart muscle. Sudden blockage of the coronary artery causes heart attack (also known as a myocardial infarction) will result in the death of heart muscle. In adults, heart muscle cannot regenerate itself effectively. The dead heart muscle is replaced by scar tissue which jeopardizes the function of the heart. Regeneration of lost heart muscle by stem cells is one strategy to restore heart function after a myocardial infarction. Embryonic stem cells (ES cell) can differentiate into heart muscle cells spontaneously or by induction with chemicals and growth factors. Thus, ES cells could be a very useful source for repairing injured heart. However, none of the current methods available can efficiently induce 100% of ES cells to differentiate into heart muscle. While, injection of a mixture of differentiated heart muscle cells and undifferentiated ES cells into the heart may cause tumor formation. Thus, we propose to develop a method to select differentiated heart muscle cells. We plan to label the ES cell derived-heart cells with a surface marker so that the differentiated heart muscle cells can be isolated from undifferentiated ES cells and other cell types. We will use adeno-associated virus (AAV) to deliver the cardiac-specific surface marker gene, because this virus is not associated with any human diseases, will not stimulate a strong immune reaction in humans and can infect undifferentiated and differentiated human ES cells. The labeled heart muscle cells will be isolated from a pool of undifferentiated ES cells and other cell types based on the specific surface marker. We will then analyze the purity and function of the isolated cells, and the ability of these cells to regenerate heart muscle. Our ultimate goal is to find an effective way to isolate pure ES cell-derived heart cells to repair damaged myocardium. This study will lead to the development of a more efficient cell therapy for coronary heart disease.
Statement of Benefit to California:
Each year, approximately 1 million Americans suffer a heart attack and 40% of them are fatal. Heart disease is America’s number one killer, claiming nearly 1400 lives daily. In California, the death rate associated with heart disease is 504/10,000 for people older than 35 (data collected in 1969-2000). A heart attack results in the death of heart muscle caused by the sudden blockage of a coronary artery by a blood clot. In adults, heart muscle cannot regenerate itself efficiently. The dead heart muscle is replaced by scar tissue, which leads to the gradual loss of heart function. Medical and surgical procedures are often needed to restore the blood supply to the remaining heart muscle and to prevent future heart attacks. However, patients usually need to take medication long-term to slow down the progressive process of the disease. Although many advanced treatments have been developed, none can cure the disease. The cost of medicine and surgery are quite high. The health care system may simply not be able to meet the needs of patients or control these spiraling costs, unless the therapeutic focus switches away from maintenance and toward its prevention and cure. The treatment and cure of heart disease can potentially be accomplished through the use of new regenerative medical therapies including a special type of human cells, called stem cells. Our research will overcome some of the obstacles and will lead to the development of an effective and safe therapeutic strategy for coronary heart disease. The results obtained from this study will eventually improve the quality of life, prolong life and reduce the burden of long-term health care for Californians.