Harnessing Epicardial Progenitor Cells and Their Derivatives for Rescue and Repair of Cardiac Tissue After Myocardial Infarction.

Abstract

Ischemic heart disease and stroke lead to the greatest number of deaths worldwide. Despite decreased time to intervention and improvements in the standard of care, 1 out of 5 patients that survive a myocardial infarction (MI) still face long-term chronic heart failure and a 5-year mortality rate of about 50%. Based on their multi-potency for differentiation and paracrine activity, epicardial cells and their derivatives have potential to rescue jeopardized tissue and/or promote cardiac regeneration. Here we review the diagnosis and treatment of MI, basic epicardial cell biology, and potential treatment strategies designed to harness the reparative properties of epicardial cells. During cardiac development, epicardial cells covering the surface of the heart generate migratory progenitor cells that contribute to the coronary vasculature and the interstitial fibroblasts. Epicardial cells also produce paracrine signals required for myocardial expansion and cardiac growth. In adults with myocardial infarction, epicardial cells and their derivatives provide paracrine factors that affect myocardial remodeling and repair. At present, the intrinsic mechanisms and extrinsic signals that regulate epicardial cell fate and paracrine activity in adults remain poorly understood. Human diseases that result in heart failure due to negative remodeling or extensive loss of viable cardiac tissue require new, effective treatments. Improved understanding of epicardial cell function(s) and epicardial-mediated secretion of growth factors, cytokines and hormones during cardiac growth, homeostasis and injury may lead to new ways to treat patients with myocardial infarction.