Effects of electrical stimulation on the cardiogenic differentiation of mesenchymal stem cells: A systematic review

Electrical stimulation has emerged as a promising strategy for promoting cardiogenic differentiation of mesenchymal stem cells; however, the available evidence remains highly heterogeneous across stimulation parameters, experimental platforms, and outcome measures. This systematic review synthesized the available in vitro evidence regarding the effects of electrical stimulation on MSC cardiogenic differentiation, with particular emphasis on stimulation parameters, experimental platforms and biological outcomes related to early cardiogenic commitment and structural maturation. A systematic search was conducted in seven electronic databases in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Fifteen preclinical in vitro studies met the eligibility criteria. Human-derived MSCs were the most frequently investigated cell source and carbon-based electrodes were the most commonly reported conductive material. Across the included studies, electrical stimulation was frequently associated with morphological changes and increased expression of markers related to early cardiogenic commitment and structural maturation, although findings were inconsistent for some outcomes. A stimulation frequency of 1 Hz, pulse widths of 5 ms, and stimulation periods of approximately two weeks were the most frequently employed conditions. Nevertheless, substantial heterogeneity in stimulation parameters, experimental platforms and outcome measures precluded direct comparisons among studies and prevented identification of an optimal stimulation protocol. Overall, the available evidence suggests that electrical stimulation may represent a promising strategy for promoting the cardiogenic differentiation of mesenchymal stem cells in vitro; however, greater methodological standardization, standardized outcome assessment and functional characterization are required before definitive conclusions regarding its effectiveness and optimal stimulation protocols can be established.

The online version contains supplementary material available at https://doi.org/10.1007/s10616-026-01065-w.