Nanosecond pulsed electric fields enhance mesenchymal stem cells differentiation via DNMT1-regulated OCT4/NANOG gene expression

Stem Cell Research & Therapy

Tong Ning¹  Zigang Ge¹  Kejia Li¹  Yangzi Jiang²  Jue Zhang³  Hao Wang⁴ 

[1] Department of Biomedical Engineering, College of Engineering, Peking University;Institute for Tissue Engineering and Regenerative Medicine, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong;Institute of Biomechanics and Biomedical Engineering, College of Engineering, Peking University;Peking-Tsinghua Center for Life Sciences, Peking University;

关键词: Mesenchymal stem cells;    Nanosecond pulsed electric fields;    Demethylation;    DNMT1;    Biophysical stimulation;    Stem cell differentiation;   

DOI  :  10.1186/s13287-020-01821-5

来源: DOAJ

【 摘 要 】

Abstract Background Multiple strategies have been proposed to promote the differentiation potential of mesenchymal stem cells (MSCs), which is the fundamental property in tissue formation and regeneration. However, these strategies are relatively inefficient that limit the application. In this study, we reported 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 genes. In order to explore the corresponding mechanism, we examined the expression of pluripotency genes and the methylation status 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-treating with 5 pulses of nsPEFs stimulation (energy levels as 10 ns, 20 kV/cm; 100 ns, 10 kV/cm), due to that the nsPEFs demethylated the promoters of stem cell pluripotency genes OCT4 and NANOG through instantaneous downregulation of DNA methylation transferase 1 (DNMT1), thereby increasing 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.

【 授权许可】

Unknown