Leveraging electric current stimulation and chemical induction to enhance MSC differentiation into cardiomyocytes

To investigate whether direct electric current stimulation, when combined with chemical induction, can enhance the cardiomyogenic differentiation of mesenchymal stem cells (MSCs), offering a potential strategy for cardiac regeneration.

Bone marrow-derived MSCs were subjected to short-term microcurrent stimulation (90 seconds) using an electroporation cuvette with voltages of 1-10 V and pulse parameters of 2 ms at 0.5-2 hz. 5-azacytidine (5-aza) was added as a chemical inducer. In vitro analyses included morphological observation, immunofluorescence staining, qPCR, and flow cytometry. In vivo, pretreated MSCs were injected into a rat myocardial infarction model.

Electrical stimulation enhanced MSC alignment and upregulated cardiomyocyte-specific markers. Gene and protein expression analyses confirmed enhanced differentiation, especially in the combined treatment group. In vivo transplantation resulted in partial restoration of myocardial architecture, though no significant ventricular wall thickening was observed within four weeks.

This study introduces a dual approach combining electrical and chemical cues to promote cardiomyogenic differentiation in MSCs. The use of a simple electroporation cuvette offers a practical and accessible method, with potential translational relevance for future cardiac repair strategies.