Physiological conditioning by electric field stimulation promotes cardiomyogenic gene expression in human cardiomyocyte progenitor cells

Aida Llucià-Valldeperas, Benjamin Sanchez, Carolina Soler-Botija, Carolina Gálvez-Montón, Santiago Roura, Cristina Prat-Vidal, Isaac Perea-Gil, Javier Rosell-Ferrer, Ramon Bragos, Antoni Bayes-Genis

The optimal cell lineage for cardiac-regeneration approaches remains mysterious. Additionally, electrical stimulation promotes cardiomyogenic differentiation of stimulated cells. Therefore, we hypothesized that electrical conditioning of cardiomyocyte progenitor cells (CMPCs) might enrich their cardiovascular potential. CMPCs were isolated from human adult atrial appendages, characterized, and electrically stimulated for 7 and 14 days. Electrical stimulation modulated CMPCs gene and protein expression, increasing all cardiac markers. GATA-binding protein 4 (GATA4) early transcription factor was significantly overexpressed (P = 0.008), but also its coactivator myocyte enhancer factor 2A (MEF2A) was upregulated (P = 0.073) under electrical stimulation. Moreover, important structural proteins and calcium handling-related genes were enhanced. The cardioregeneration capability of CMPCs is improved by electrical field stimulation. Consequently, short-term electrical stimulation should be a valid biophysical approach to modify cardiac progenitor cells toward a cardiogenic phenotype, and can be incorporated into transdifferentiation protocols. Electrostimulated CMPCs may be best-equipped cells for myocardial integration after implantation.