Recent developments in cardiovascular stem cells.

Abstract

Heart failure, a common consequence of ischemic heart disease, is a major cause of morbidity and mortality in the world.1–3 Pharmacological treatment with β-blockers and inhibitors of the renin–angiotensin–aldosterone system has improved the clinical outcomes in patients with heart failure.4–7 Likewise, mechanical unloading with left ventricular assist devices and resynchronization therapy have led to partial reversal of cardiac structural and molecular remodeling and symptomatic improvement.8–10 Despite these remarkable advances, however, mortality and morbidity of patients with heart failure, with or without reduced ejection fraction remains high.1,2 Moreover, heart transplantation, while an effective option, is available only for a selected number of patients and is not without considerable negative consequences.11 Furthermore, gene therapy still remains in early investigational stages and not yet ready for clinical applications.12 The high residual mortality and morbidity of patients with heart failure might be inherent to the shortcomings of the current therapeutic approaches, as none directly targets the underlying causal problem in heart failure, that is, loss of or intrinsically dysfunctional myocytes. Consequently, novel therapeutic approaches are necessary to further improve the clinical outcomes in patients with heart failure. The heart is considered, by and large, a terminally differentiated organ with a limited intrinsic regenerative capacity that alone is insufficient to compensate for the pathological loss of cardiac myocytes during the postnatal period.13–15 The discovery of cardiac progenitor cells (CPCs) in the heart more than a decade ago along with the recent data showing that the existing myocytes undergo a gradual turnover have raised the potentials for regenerative cardiac repair.16,17 Likewise, the discovery of mesenchymal stem cells (MSCs), which was thought to have the potential to differentiate to cardiac myocytes, but yet to proven, or enhance …