Abstract
Background: Multiple strategies have been proposed to promote the differentiation potential of MSCs, which is the fundamental property in tissue formation and regeneration. However, these strategies are relatively inefficient that limit the application, thus more advanced methods are needed. In this study, we report a novel and efficient strategy, nanosecond pulsed electric fields (nsPEFs) stimulation, which can enhance the trilineage differentiation potential of MSCs; and further explained the mechanism behind. Methods: We used histological staining to screen out the nsPEFs parameters that promoted the trilineage differentiation potential of MSCs, and further proved the effect of nsPEFs by detecting the functional gene. In order to explore the corresponding mechanism, we examined the expression of pluripotency genes and the methylation of their promoters. Finally, we targeted the DNA methyltransferase which was affected by nsPEFs. Results: The trilineage differentiation of bone marrow derived MSCs was significantly enhanced in vitro by simply pre-treated with 5 pulses of nsPEFs stimulation (energy levels as 10 ns, 20 kV/cm; 100 ns, 10 kV/cm), and this was due to the nsPEFs demethylated the promoters of stem cell pluripotency genes OCT4 and NANOG through instantaneous downregulation of DNA Methylation Transferase 1 (DNMT1), thereby increased the expression of OCT4 and NANOG for up to 3 days, and created a treatment window period of stem cells. Conclusions: In summary, nsPEFs can enhance MSCs differentiation via the epigenetic regulation, and could be a safe and effective strategy for future stem cell application.
Nanosecond pulsed electric fields enhance chondrogenesis of mesenchymal stem cells (MSCS) partially via phosphorylation of P38-MAPK