Cardiac pre-differentiation of human mesenchymal stem cells by electrostimulation

Myocardial repair using stem-cell therapy has become a promising therapeutic tool. However, many questions concerning a precise functional integration of injected cells remain unanswered. The use of cardiac precommitted cells may improve integration, as these cells may complete their differentiation in the myocardium reducing fibrosis and restoring muscle function. We have previously demonstrated that electrostimulation (ES) induces cardiomyocyte pre-commitment of fibroblasts in vitro and is an effective alternative to cytokine-induced differentiation. In this study, we evaluated the effects of long term electrostimulation on human mesenchymal stem cells (hMSCs). ES induced both morphological and biochemical changes in hMSCs resulting in a shift toward a striated muscle cell phenotype expressing cardiac specific markers. This partially differentiated phenotype might allow a gradual, ongoing differentiation within the cardiac environment, providing time for both myocardial regeneration and electro-mechanical integration, and convey potential advantages in clinical applications.