Specific Intensity Direct Current (DC) Electric Field Improves Neural Stem Cell Migration and Enhances Differentiation towards βIII-Tubulin+ Neurons

Abstract

Control of stem cell migration and differentiation is vital for efficient stem cell therapy. Literature reporting electric field–guided migration and differentiation is emerging. However, it is unknown if a field that causes cell migration is also capable of guiding cell differentiation—and the mechanisms for these processes remain unclear. Here, we report that a 115 V/m direct current (DC) electric field can induce directional migration of neural precursor cells (NPCs). Whole cell patching revealed that the cell membrane depolarized in the electric field, and buffering of extracellular calcium via EGTA prevented cell migration under these conditions. Immunocytochemical staining indicated that the same electric intensity could also be used to enhance differentiation and increase the percentage of cell differentiation into neurons, but not astrocytes and oligodendrocytes. The results indicate that DC electric field of this specific intensity is capable of promoting cell directional migration and orchestrating functional differentiation, suggestively mediated by calcium influx during DC field exposure.

Glial responses to implanted electrodes in the brain

“…In the context of neurogenesis, neuromodulation is gaining traction as a reparative tool for brain injury and disease 118,134 . Neurostimulation stimulates neural progenitor proliferation 135–137 , directs the migration (galvanotaxis) of neuronal and glial precursors 134,138–140 and promotes their differentiation 136,137,140,141 . Interestingly, tDCS-polarized proinflammatory microglia accompany NG2-precursor migration to promote functional recovery after stroke 130 .…”

Regulation of adipose‐tissue‐derived stromal cell orientation and motility in 2D‐ and 3D‐cultures by direct‐current electrical field

“…; Zhao et al . , ), which corresponds to an EF strength of about 5 V/cm in vitro . Wounding the corneal epithelium disrupts tight junctions among the cells that normally help maintain the potential difference.…”

“…Our experimental results are in agreement with the literature (Hammerick et al 2010b). Many ª 2017 Japanese Society of Developmental Biologists studies have confirmed that a 50 lm of mammalian corneal epithelium exhibits approximately 25 mV transepithelial potential difference across (Hammerick et al 2010b;Zhao et al 2011Zhao et al , 2015, which corresponds to an EF strength of about 5 V/cm in vitro. Wounding the corneal epithelium disrupts tight junctions among the cells that normally help maintain the potential difference.…”

“…Fields of this magnitude can direct corneal epithelial cell orientation and migration, enhancing corneal epithelial wound healing. Over 10 kinds of cells, including corneal epithelial, lens epithelial, vascular endothelium, nerve, mesenchymal cells as well as keratinocytes, osteoblasts and fibroblasts, show galvanotaxis through directional migration movements toward the EF cathode and vertical alignment to the EF vector (Hammerick et al 2010b;Zhao et al 2011Zhao et al , 2015. Although the result of 2D experiments did not elicit any new cellular phenomena, it was helpful to verify the effectiveness of our electrical stimulation method and the galvanotaxis of ADSCs.…”

“…; Zhao et al . , ). Although the result of 2D experiments did not elicit any new cellular phenomena, it was helpful to verify the effectiveness of our electrical stimulation method and the galvanotaxis of ADSCs.…”