Heart disease is the number one cause of death and a leading cause of disability in the California. About 40,000 heart attack victims are admitted to California hospitals annually, and over 5,000 of these patients die. When a heart attack occurs, blood flow to the heart muscle is cut off, and eventually portions of the muscle of the heart die and are replaced by non-contracting scar tissue. Heart muscle does not adequately regenerate. In this proposal we hypothesize that the beating, immature cardiac cells derived from human embryonic stem cells can be injected directly into the heart attack scar, and that these cells will survive, grow, develop their own blood supply and eventually improve the contractile function of the entire heart. Improved contraction would help reduce the possibility of heart failure, dilatation of the ventricle and possible death. Before human embryonic stem cells can be injected into a human heart, these cells will need to be tested in standardized animal models. The rat heart attack, which we propose to use in this series of studies, is a standard, well characterized model with many factors in common with heart attacks in humans. Our proposal should help to answer the question of whether an injured heart can be rebuilt using human embryonic stem cells. Our proposal will also test the mechanisms by which treatment with human embryonic stem cell therapy may be beneficial: examining whether the injected cells couple electrically with host cells and/or whether the injected stem cells produce humoral factors that may benefit the function of the host heart.
Statement of Benefit to California:
Heart disease is the number one cause of death and a leading cause of disability in the State of California. Approximately 40,000 heart attack victims are admitted to California hospitals annually, and over 5,000 of these patients die. Heart attacks occur when an atherosclerotic plaque ruptures within a coronary artery. A blood clot forms and cuts off additional flow of blood to the muscle of the heart. Heart cells do not receive enough oxygen and nutrients and these heart cells die. In general, heart cells do not regenerate and following a heart attack, dead heart muscle is replaced by a thin, collagenous, non-contracting scar. The purpose of our study will be to determine whether immature heart cells derived from human embryonic stem cells can replace the scar with viable beating muscle. If the heart can be rebuilt with cells derived stem cells, this has the potential to reduce suffering, disability, and death associated with one of the most common causes of illness and death in the State of California.