Cardiac Regenerative Therapy Using Gene-Edited Stem Cells to Improve Transplantation Outcomes
NIH
UNIVERSITY OF CALIFORNIA AT DAVIS
Cardiovascular disease is the leading cause of morbidity and mortality in the United States. A significant loss of cardiomyocytes from myocardial infarction (MI) can result in progressive deterioration of cardiac function. Many patients do not recover their cardiac function despite optimal medical therapies and develop progressive adverse structural and electrical remodeling leading to heart failure (HF) with lethal consequences. HF remains a deadly clinical syndrome with 5-year mortality of 45–60%. Therefore, there is a compelling need to seek new options for patients in end-stage HF. Since adult cardiac myocytes are unable to proliferate sufficiently to replace the damaged tissue, stem cell therapy represents a new promising approach for the treatment of end-stage HF, since it aims at generating new functional myocardium and inducing neoangiogenesis. However, one of the main challenges of cardiac stem cell transplantation is the survival and retention of transplanted cells in the hostile milieu. We have recently published compelling data to demonstrate the one of the main causes of transplanted stem cell loss is inflammation in a murine post-MI model. Therefore, the overarching goal of this proposal is to target genes involved in the inflammatory pathway in somatic cells that will be transplanted, to improve transplantation outcomes in end-stage HF. The proposal addresses the critical role of inflammation induced-cell death that severely impede cardiac stem cell therapy. Successful completion will pave way to facilitate future personalized cardiovascular care for patients with end-stage HF and the translation of transplantation therapies from bench side to clinical practice. The proposed study will provide an impactful new therapeutic option for the treatment of end-stage heart failure. The outcome of this study will overcome two critical barriers for the treatment of heart failure namely inflammation and inflammation-linked cell death that hinder the successful clinical translation of stem cell therapy.
Non-SBIR/STTR