Highly specific differentiation of MSCs into neurons directed by local electrical stimuli triggered wirelessly by electromagnetic induction nanogenerator

Abstract

Transdifferentiation of mesenchymal stem cells (MSCs) into neurons provides a practical way for neurodegenerative diseases as alternatives to neural stem cells, but is confronted with challenges to get well-differentiated and mature neurons. In this work, a wirelessly triggered local electrical stimulation system was established to specifically induce neuronal differentiation from rat bone-marrow-derived MSCs (rBMSCs) by coupling a highly conductive and flexible multi-wall carbon nanotube (MWCNT) membrane with a rotating magnetic field. Without nerve-inducing factors, a nearly 100% yield of differentiated neurons was realised without the presence of astrocyte cells by the localized electrical stimuli mediated from electromagnetic induction nanogenerator. Neuronal functions were revealed by rapid spontaneous [Ca2+] i-transient peaks under neurotransmitter action. This novel therapeutic strategy for neurodegenerative disease was further demonstrated in vivo, where the successful neural differentiation of exogenous rBMSCs driven by external magnetic-filed accelerated the brain recovery. This wireless electric stimulation system shows promising effects on neuron differentiation and offers a new perspective in nerve repair without glial scarring.