Cardiovascular disease is the leading cause of death and disability in the United States. Cell transplantation using the patients’ own cells (autologous cells) to repair the heart is a promising new approach with the potential to treat the millions of patients with debilitating heart conditions. Current therapies do not restore the function of the scarred area after myocardial infarct. Through stem cell research, it has been shown that the heart itself contains a repository of stem and progenitor cells that have the unique ability to give rise to cardiomyocytes, endothelial cells and vascular smooth muscle cells, all of which collectively contribute to repairing damaged heart tissue. These cells have gained considerable interest because recent studies have shown that other autologous sources, such as the bone marrow, have not been as effective as originally hoped for regeneration of the heart in early clinical trials. In order to determine the best way to harness this population of resident cells to help patients with heart disease, the methodology to reproducibly isolate and expand the cells must be developed in the laboratory and they must be shown to be both effective in the long term and safe for clinical use. Our research group is a highly interactive team of surgeons, clinicians and basic scientists who are working together to identify new ways to help both children and adults with heart disease by developing methods to use the patients’ own cells to identify new therapies that are both effective and safe. We have recently identified markers that can be used to sort the progenitor cells that are needed for cardiac repair and now propose to optimize the conditions that will allow us to expand these cells to sufficient numbers for transplantation and carefully test long term function in preclinical models.
Heart attacks are one of the leading causes of death in California. The California Office of Statewide Health Planning recently estimated that approximately 40,000 heart attack patients are admitted to California hospitals annually. These statistics are further supported by a study from the California Health Care Foundation which concluded that heart disease and hypertension (leading to heart disease and stroke) represent two of the four most common chronic health conditions in this state. Heart disease and the associated costs of treating these patients are unquestionably a significant public health challenge. The most recent estimates suggest that costs of annual health care for California residents with heart disease are about $12,900 per capita, over five times the health care costs of the general adult population. It would benefit the residents of this state, and the general population, if scientists could develop new and cost-efficient treatments for patients with heart disease. Recent advances in the field of stem cell research have led to the identification of progenitor cells that can be expanded from the patients’ own cells. Our research team of surgeons, cardiologists and basic scientists have identified a population of progenitor cells that can be isolated from autologous heart tissue and/or from re-programmed differentiated human cells. The research that we propose to do will identify new and improved ways to expand these cells for transplantation into the heart and optimize the conditions that promote cardiac regeneration in a safe and effective manner. The benefit of these proposed studies includes improved quality of life for patients and their families. Improved patient outcome will be translated into reduced costs of medical care. The technology associated with developing new methods for expansion and use of these cells, in partnership with industry, has the potential to bring new revenue to the state and to research institutions. This will enhance the opportunities for the education and training of new scientists and the recruitment of established investigators to educational centers of higher learning in the state of California.