Electrical stimulation at nanoscale topography boosts neural stem cell neurogenesis through the enhancement of autophagy signaling

Neural stem cells (NSCs) transplantation at the injury site of central nerve system (CNS) makes it possible for neuroregeneration. Long-term cell survival and low proliferation, differentiation, and migration rates of NSCs-graft have been the most challenging aspect on NSCs application. New multichannel electrical stimulation (ES) device was designed to enhance neural stem cells (NSCs) differentiation into mature neurons. Compared to controls, ES at nanoscale topography enhanced the expression of mature neuronal marker, growth of the neurites, concentration of BDNF and electrophysiological activity. RNA sequencing analysis validated that ES promoted NSC-derived neuronal differentiation through enhancing autophagy signaling. Emerging evidences showed that insufficient or excessive autophagy contributes to neurite degeneration. Excessive ES current were able to enhance neuronal autophagy, the neuronal cells showed poor viability, reduced neurite outgrowth and electrophysiological activity. Well-controlled autophagy not only protects against neurodegeneration, but also regulates neurogenesis. Current NSC treatment protocol efficiently enhanced NSC differentiation, maturation and survival through combination of proper ES condition followed by balance of autophagy level in the cell culture system. The successful rate of such protreated NSC at injured CNS site should be significantly improved after transplantation.