Cellular cardiomyoplasty, which involves the transplantation of exogenous cells into the heart, is a promising approach to repair injured myocardium and improve cardiac function. We have isolated a population of muscle-derived stem cells (MDSCs) from the skeletal muscle of both mice and human, that when compared with myoblasts, display a significantly improved capacity for regeneration in a model of acute myocardial infarction (MI). The transplanted MDSCs survive significantly better than skeletal myoblasts, and through a paracrine effect, reduce myocardial fibrosis, promote angiogenesis, and ameliorate left ventricular (LV) remodeling. We have reported that the improved survival of MDSCs in acute MI is related, at least in part, to their high expression of cellular antioxidants which give the MDSCs the unique ability to resist oxidative and inflammatory stress, conditions likely experienced by these cells after their implantation into infarcted myocardium. Although these findings suggest that both murine and human MDSCs represent a therapeutic cell source for MI patients, important limitations, such as the poor delivery approach (intracardiac injection), as well as the low cardiomyogenic potential of MDSCs, have limited the cardiac regenerative potential repair of MDSCs. In fact, we have been utilizing MDSCs for the repair of a variety of tissues, and the MDSCs were always delivered directly into the injured hearts. The use of the innovative FGF2-coacervate as a novel delivery approach represents a new area of research that can further promote the cardiac regenerative potential of MDSCs. In fact, using this innovative coacervate approach, we have shown that FGF-2- coacervate was able to enhance cardiac repair and regeneration by promoting angiogenesis. Therefore, we will present recent work from our laboratory where we combine the new FGF2 coacervate technology with MDSCs to further improve cardiac repair when compared to the intracardiac injection of MDSCs. We will also present recent work from our group where the cell sheet technology will be combined with MDSCs to further improve the regenerative potential of MDSCs in the hearts. Finally, we will present recent work where the viral transduction of MDSCs to express Wnt-11, a molecule required for cardiogenesis , enhance the cardiomyogenic differentiation of the MDSCs in vitro, and cardiac repair in vivo, when injected directly into the injured hearts. This new technology will not only increase our understanding of the basic biology of muscle-derived progenitor cell populations with enhanced cardiomyogenic potential for cardiac repair, but also facilitate the development of new delivery technologies based on biomimetic coacervate to improve cardiac regeneration and repair induced by cellular cardiomyoplasty using muscle progenitor cells.