CHAPTER 2: Challenges in stem cell-based approaches for myocardial regeneration after myocardial infarction

Myocardial infarction is the leading cause of chronic heart failure, an ominous disease entity with a wide prevalence in many countries. The morbidity and mortality of chronic heart failure remains high, despite recent pharmacologic advances and cardiac resynchronization therapy. After acute coronary occlusion, the necrotic area triggers a cascade of pathophysiologic events that may lead to structural and electrophysiological left ventricular remodeling, and eventually to progressive chronic heart failure. Therapeutic strategies targeting the repair of the infarcted myocardium aim at interrupting this vicious cycle and constitute an etiological and, as such, promising approach. However, after the initial enthusiasm accompanying early reports, subsequent preclinical and clinical studies unveiled several challenges associated with cell survival and proliferation, as well as abnormal electrophysiological responses after engraftment. In this chapter, we review the main cell sources that hold promise for clinical use, either alone or combined with growth factors and biomaterials, focusing on the acute and medium-term electrophysiological effects of cardiac regeneration approaches.