Human Embryonic Stem Cells for Heart Failure

Funding Type: 
Disease Team Planning
Grant Number: 
ICOC Funds Committed: 
Public Abstract: 

Heart disease is the number one cause of death and a leading cause of disability in California. About 40,000 heat attack victims are admitted to California hospitals annually and over 5000 of these patients die. Many suffer the symptoms of heart failure including shortness of breath and fatigue, which reduce quality of life and cause disability and unemployment. Heart failure occurs when the heart cannot pump blood at a volume adequate to meet the metabolic needs of tissues of the body. While there are numerous causes of heart failure, two of the biggest are loss (death) of heart muscle due to heart attack and global weakness of the heart muscle (cardiomyopathy). Our research group has clearly shown that it is possible to rebuild a damaged heart. In studies of rats with heart attacks, injections of immature beating heart cells from neonatal or fetal rats replenished the noncontracting scar with viable heart muscle and resulted in long term improvement in heart function. Results with bone marrow derived stem cells resulted in some transient benefit in heart function. Our recent study with immature heart cells derived from human embryonic stem cells injected directly into diseased hearts appears promising. We were able to show that these stem cells could survive in a damaged heart, continue to mature and develop the proteins needed for healthy contraction, that the proteins were organized into the contractile units needed for heart functioning, and that these cells could integrate with surrounding host cells. The purpose of our Disease Team Planning Award is to develop a plan involving talent from a number of {REDACTED} California institutions to identify the additional preclinical studies that need to be accomplished in order to take human embryonic stem cell therapy into clinical practice and then develop initial clinical trials to test human embryonic stem cell therapy in patients with heart failure due to heart attack or cardiomyopathy. A team approach will be utilized in which one group of specialists will develop the cells to be used, a second group will test these cells in animal models of disease, a third group will develop protocols to test the cells in patients with heart failure; a fourth will deal with regulatory issues, and fifth will be an outside advisory committee. Over the six month planning period the team will meet frequently. The Principal Investigator will be the team leader who will coordinate the efforts of the specialists. The collaborative effort will involve the following institutions: {REDACTED}, {REDACTED}, {REDACTED}, {REDACTED} and {REDACTED}, with consultants on regulatory matters from {REDACTED}.

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 flow of blood to the heart muscle. The heart muscle cells die and are replaced by thin, collagenous, non-contracting scar. This loss of heart cells may lead to death of the patient or heart failure in which the heart cannot pump enough blood to meet the metabolic demand of the body’s tissues. Heart failure is also a common manifestation of a disease called cardiomyopathy. Cardiomyopathy occurs when there is a global weakness of all the heart cells in the main pumping chamber of the heart. The problem of heart failure due to heart attack or cardiomyopathy has the potential to be solved by injecting immature heart cells derived from human embryonic stem cells into the scar or the diseased heart tissue. We have shown in our laboratory of the {REDACTED} that these cells can replace the diseased tissue with healthy contracting heart cells. However, there are a number of technical and scientific hurdles that must be overcome before this therapy can be applied to patients. The purpose of the CIRM Disease Planning Award will be to create a team of specialists from a number of medical institutions in {REDACTED} California {REDACTED}, {REDACTED}, {REDACTED}, {REDACTED} in order to develop preclinical protocols that show a benefit of stem cell transplantation on cardiac function in models of heart attack and dilated cardiomyopathy and then apply that knowledge to clinical trials. Ultimately, this form of therapy has the potential to benefit the State of California by reducing the degree of suffering due to heart failure, reducing disability, reducing missed work days, and reducing death associated with heart failure due to heart attack or cardiomyopathy. These benefits for the State would therefore be humanitarian in easing death and suffering while improving the quality of life, as well as economic by reducing disability, visits to the emergency ward and hospital, and improving ability to work.