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.

Highlights

  • The adult human brain contains several regions capable of producing neuronal stem/progenitor cells, including the forebrain’s anterior subventricular zone (SVZ) and hippocampus

  • We report that 115V/m direct current (DC) electric field can induce neural stem cell migration in vitro in a calcium-dependent manner

  • Using multi-dimentional approaches, including intra- and extracellular calcium buffering and live cell imaging, we report that a 115 V/m DC electric field can enhance mobility and cause cathodal migration in the cultured neural precursor cells (NPCs) via a calcium-mediated mechanism

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Summary

Introduction

The adult human brain contains several regions capable of producing neuronal stem/progenitor cells, including the forebrain’s anterior subventricular zone (SVZ) and hippocampus. These areas provide valuable resources for neural regeneration. To compensate for the limited availability of stem cells for neurogenesis, laboratory studies are focusing on direct transplantation of cultured adult NPCs into the injured area. This approach has been reported successful in promoting the formation of new nerve cells, it is generally accepted that transplanted cells experience great difficulty migrating and PLOS ONE | DOI:10.1371/journal.pone.0129625. This approach has been reported successful in promoting the formation of new nerve cells, it is generally accepted that transplanted cells experience great difficulty migrating and PLOS ONE | DOI:10.1371/journal.pone.0129625 June 11, 2015

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