Regulation of Neural Differentiation of ADMSCs using Graphene-Mediated Wireless-Localized Electrical Signals Driven by Electromagnetic Induction

Although adipose-derived mesenchymal stem cells (ADMSCs) isolated from patients' fat are considered as the most important autologous stem cells for tissue repair, significant difficulties in the neural differentiation of ADMSCs still impede stem cell therapy for neurodegenerative diseases. Herein, a wireless-electrical stimulation method is proposed to direct the neural differentiation of ADMSCs based on the electromagnetic effect using a graphene film as a conductive scaffold. By placing a rotating magnet on the top of a culture system without any inducer, the ADMSCs cultured on graphene differentiate into functional neurons within 15 days. As a conductive biodegradable nanomaterial, graphene film acts as a wireless electrical signal generator driven by the electromagnetic induction, and millivolt-level voltage generated in situ provokes ADMSCs to differentiate into neurons, proved by morphological variation, extremely high levels of neuron-specific genes, and proteins. Most importantly, CA²⁺ intracellular influx is observed in these ADMSC-derived neurons once exposure to neurotransmitters, indicating that these cells are functional neurons. This research enhances stem cell therapy for neurodegenerative diseases using autologous ADMSCs and overcomes the lack of neural stem cells. This nanostructure-mediated physical-signal simulation method is inexpensive, safe, and localized, and has a significant impact on neural regeneration.