Optimization of Stem Cell Therapies for Coronary Collateral Growth in Cardiovascular Disease

Ischemic heart disease is a leading cause of death around the world. Coronary collateral growth occurs as a natural, adaptive response to myocardial ischemia, and provides an alternate path for blood to flow to the area at risk. Many patients with ischemic heart disease demonstrate insufficient collateral growth and thus remain at high risk for myocardial infarction and heart failure. Stem cell therapies may have the potential to augment collateral growth in these patients. However, clinical trials using stem cells to increase myocardial blood flow have shown minimal benefit. Perhaps the harsh, oxidative environment into which stem cells are administered may contribute to excessive cell death prior to achieving a therapeutic effect. These experiments are based upon the overall hypothesis that stem cells conditioned to withstand oxidative stress in culture will produce greater increases in coronary collateral growth upon delivery in vivo.