Cell transplantation to repair or regenerate injured myocardium is a new 
frontier in the treatment of cardiovascular disease. Most studies on stem cell 
transplantation therapy in both experimental heart infarct and in phase-I human 
clinical trials have focused on the use of undifferentiated stem cells. Based on 
our previous observations demonstrating the presence of multipotent progenitor 
cells in human adult skeletal muscle, in this study we investigated the capacity 
of these progenitors to differentiate into cardiomyocytes. Here we show an 
efficient protocol for the cardiomyogenic differentiation of human adult 
skeletal muscle stem cells in vitro. We found that treatment with Retinoic Acid 
directed cardiomyogenic differentiation of skeletal muscle stem cells in vitro. 
After Retinoic Acid treatment, cells expressed cardiomyocyte markers and 
acquired spontaneous contraction. Functional assays exhibited cardiac-like 
response to increased extracellular calcium. When cocultured with mouse 
cardiomyocytes, Retinoic Acid-treated skeletal muscle stem cells expressed 
connexin43 and when transplanted into ischemic heart were detectable even 5 
weeks after injection. Based on these results, we can conclude that human adult 
skeletal muscle stem cells, if opportunely treated, can transdifferentiate into 
cells of cardiac lineage and once injected into infarcted heart can integrate, 
survive in cardiac tissue and improve the cardiac function.