Role of small molecules in the cardiac differentiation of mesenchymal stem cells

Globally, coronary heart disease is a major life-threatening degenerative disease. The molecular and cellular events in the ischemic myocardium culminate in necrosis of the tissue architecture in the infarct area which eventually leads to heart failure. As current therapeutic approaches are limited in preventing ventricular remodeling following myocardial infarction (MI), a novel therapeutic approach of transplantation of exogenously differentiated cardiomyocytes could be a better option. Mesenchymal stem cells (MSCs) have been used for the treatment of MI to repair the injured myocardium and improve cardiac function as these cells possess the ability to differentiate into multiple lineages in vitro and in vivo. However, donor cells have limited capacity to differentiate into functional cardiomyocytes in the ischemic microenvironment of the heart. Among other strategies, small molecules have been identified that promote differentiation of MSCs into functionally active cardiac-like cells. One of the best studied examples is that of the demethylating agent, 5-azacytidine and its analogues. Other synthetic and naturally occurring compounds have also been tested and were found to be good candidates for future cell-based therapeutics against cardiovascular diseases. In this chapter, potential role of small molecules on the cardiac differentiation of MSCs will be highlighted.