Cardiac Reprogramming with Stem Cells: An Advanced Therapeutic Strategy in Advanced Heart Failure

Abstract

Heart failure (HF) remains the most prominent cause of cardiovascular morbidity and mortality. The underlying molecular mechanisms of the natural evolution of HF affect cardiac myocytes’ loss and extracellular matrix rearrangement, resulting from the persistence of several etiological factors, including coronary artery disease, viral infections, epigenetic alterations, genetic mutations, adverse immune reactions, and primary cardiac toxicity. Although there are well-developed approaches to pharmacological therapy and device care, i.e., bridge-to-destination, bridge-to-bridge, and bridge-to-transplantation therapies, the mortality from advanced HF is still unacceptably high. Current efforts to improve clinical outcomes for these patients are attributed to translational medical care, which mainly directs to cardiac regeneration and reprogramming with stem cells. Recent studies in patients with ischemia and non-ischemia severe HF have shown conflicting survival results after implantation of bone marrow mesenchymal stem cells and human induced pluripotent stem cells. Still, cardiac function was substantially improved in the majority of the investigations. It has been disputed that improving stem-derived cardiac cell maturation before implantation and using alternative endogenous sources for stem cells, i.e., endogenous skeletal myoblasts, may accelerate morphofunctional recovery after implantation. Indeed, direct cardiac reprogramming has been considered a promising therapeutic approach to rejuvenate damaged myocardium by previously transforming endogenous skeletal myoblasts into cardiac myocyte-like cells. This approach being occurred to be substantially progressive is now under scientific discussion. The chapter depicts the challenging clinical perspectives for implanting cardiac reprogrammed stem cells in severe HF.