Stem cell therapy for chronic heart failure: lessons from a 15-year experience

Although cell therapy has entered the clinical arena since 2000, its benefits are still controversial. This is partly due to a shift of the whole paradigm from the mere provision of new cells intended to replenish the pool of dead cardiomyocytes to the exploitation of the cell's paracrine effects to activate host-associated cytoprotective signalling pathways, particularly those involved in angiogenesis, prevention of apoptosis and possibly recruitment of endogenous cells capable to mature into functional cardiomyocytes. This review will discuss how these two basic mechanisms (direct donor cell-derived myocardial regeneration versus paracrine signalling) underlie the rational selection of cells in light of the target clinical indication, with a particular focus on chronic heart failure, and will emphasize the importance of optimizing cell delivery and survival to fully exploit the potential benefits of this novel approach to acute and chronic heart diseases.