Charge-Balanced Electrical Stimulation Can Modulate Neural Precursor Cell Migration in the Presence of Endogenous Electric Fields in Mouse Brains

Electric fields (EFs) can direct cell migration and are crucial during development and tissue repair. We previously reported neural precursor cells (NPCs) are electrosensitive cells that can undergo rapid and directed migration towards the cathode using charge-balanced electrical stimulation in vitro. Here, we investigate the ability of electrical stimulation to direct neural precursor migration in mouse brains in vivo. To visualize migration, fluorescent adult murine neural precursors were transplanted onto the corpus callosum of adult male mice and intracortical platinum wire electrodes were implanted medial (cathode) and lateral (anode) to the injection site. We applied a charge-balanced biphasic monopolar stimulation waveform for three sessions per day, for 3 or 6 d. Irrespective of stimulation, the transplanted neural precursors had a propensity to migrate laterally along the corpus callosum, and applied stimulation affected that migration. Further investigation revealed an endogenous EF along the corpus callosum that correlated with the lateral migration, suggesting that the applied EF would need to overcome endogenous cues. There was no difference in transplanted cell differentiation and proliferation, or inflammatory cell numbers near the electrode leads and injection site comparing stimulated and implanted non-stimulated brains. Our results support that endogenous and applied EFs are important considerations for designing cell therapies for tissue repair in vivo.