Early Translational II
ICOC Funds Committed:
Five million people in the United States suffer with heart failure, resulting in ~60,000 deaths at a cost of $30 billion/year. These patients also are more prone to sudden cardiac death, causing ~500,000 deaths annually. In addition, ~80,000 children are born each year in the United States with congenital heart disease, the most common human birth defect, and many of these children eventually develop heart failure. Heart failure occurs when the heart is damaged and becomes unable to meet the demands placed on it. Unlike other organs, the heart is unable to fully repair itself after injury. Despite advances over the past two decades, it is rarely possible to rescue heart muscle from some degree of irreversible injury and death after a heart attack, and none of the currently accepted therapies replace damaged heart muscle with new heart cells. Human embryonic stem cells (hESCs) grow and divide indefinitely while maintaining the potential to develop into many tissues of the body, including heart muscle. They provide an unprecedented opportunity to advance new cell-based therapies for heart attack and heart failure. We have identified a human stem cell that gives rise to many of the types of muscle cells in the heart. In this proposal, we will test whether this cell can be used to repair damaged heart muscle in a heart attack model in the pig that closely resembles the human disease. We will develop methods to increase the local retention and survival of these cells after delivery into the heart; determine ways to prevent the body from rejecting these cells; and assess the safety of these cells with regard to heart function, rhythm and tumor formation. These studies may also generate solutions that will allow us to bring hESC therapy not only to heart attack victims, but to those bearing the burden of other diseases where organs are damaged or not functioning properly.
Statement of Benefit to California:
Heart failure is very common with ~100,000 people in California suffering from this condition at a cost of ~$540 million/year. In addition, ~11,000 children are born in California each year with congenital heart disease, the most common human birth defect. Many will develop heart failure at an additional cost of ~$75 million/year. Heart failure occurs when the heart is damaged and becomes unable to meet the demands placed on it. Unlike other organs, the heart is unable to repair itself. Our group has identified a human stem cell that gives rise to many of the types of muscle cells in the heart. The current proposal will move our group’s accomplishments forward by testing whether this cell can be used to repair damaged heart muscle in a heart attack model in the pig that closely resembles the human disease. To this end, we have assembled a multidisciplinary team of seasoned co-investigators, including cell biologists, immunologists, biomedical engineers, cardiologists, and electrophysiologists, to successfully address the Aims in this proposal, and pave the way for advancing this novel therapy to patients. In addition to the health benefits to the people of California, and the anticipated savings in health care costs, these studies will lead to therapeutic technologies that could be used by the state and its biopharmaceutical industry to increase its tax base. This research also will push the field of regenerative medicine forward despite the paucity of federal funds for early translational research.