The Quest for the Adult Cardiac Stem Cell

Over the past 2 decades, cardiac regeneration has evolved from an exotic fringe of cardiovascular biology to the forefront of molecular, genetic, epigenetic, translational, and clinical investigations. The unmet patient need is the paucity of self-repair following infarction. Robust regeneration seen in models such as zebrafish and newborn mice has inspired the field, along with encouragement from modern methods that make even low levels of restorative growth discernible, changing the scientific and technical landscape for effective counter-measures. Approaches under study to augment cardiac repair complement each other, and encompass grafting cells of diverse kinds, restarting the cell cycle in post-mitotic ventricular myocytes, reprogramming non-myocytes, and exploiting the dormant progenitor/stem cells that lurk within the adult heart. The latter are the emphasis of the present review. Cardiac-resident stem cells (CSC) can be harvested from heart tissue, expanded, and delivered to the myocardium as a therapeutic product, whose benefits may be hoped to surpass those achieved in human trials of bone marrow. However, important questions are prompted by such cells' discovery. How do they benefit recipient hearts? Do they contribute, measurably, as an endogenous population, to self-repair? Even if "no," might CSCs be targets for activation in situ by growth factors and other developmental catalysts? And, what combination of distinguishing markers best demarcates the cells with robust clonal growth and cardiogenic potential?