Year 3

Coronary artery disease (CAD) remains the leading cause of morbidity and mortality worldwide and is predicted to be the leading cause of death by 2020. In the US, it is estimated that cardiovascular disease affects 60 million patients costing the healthcare system approximately $186 billion annually. Approximately two-thirds of patients sustaining a myocardial infarction do not make a complete recovery and often are left with debilitating congestive heart failure. Despite the advances in medical treatment and interventional procedures to reduce mortality in patients with CAD, the number of patients with refractory myocardial ischemia and congestive heart failure is rapidly increasing. For end-stage heart failure, heart transplantation is the only successful treatment. However, the ability to provide this treatment is limited by the availability of donor hearts. Therefore, alternative therapies in the prevention and treatment of end-stage heart failure are needed.

Critical to any heart repair strategy is the need to provide vessels to allow for an adequate blood supply to nourish the heart. Our results demonstrate that human embryonic stem cell (hESC)-derived hemangioblasts can create new blood vessels and improve blood flow in a rodent model of myocardial infarction. Studies are in progress to improve the efficiency and effectiveness of hESC-derived hemangioblasts to create new blood vessels. Strategies to improve efficiency and effectiveness include the use of extracellular matrix proteins (components that make up the structural aspect of the heart) to increase the survival of the cells or the use of antibodies to direct and link the cells to the damaged heart muscle. Additionally, to decrease the risk of tumor formation from the hESC-derived hemangioblasts, the hESC-derived hemangioblasts are being cultured to form more mature endothelial cells (cells that mimic the bodies natural cells that produce blood vessels). These cells are being tested to determine whether they can effectively induce blood vessels in the heart. Our initial finding of hES-derived hemangioblasts inducing new blood vessel formation may eventually lead to the development of an unlimited and reliable cell source for renewing blood vessels and treating myocardial infarction.