Abstract

BackgroundThe existence of neural stem and progenitor cells (together termed neural precursor cells) in the adult mammalian brain has sparked great interest in utilizing these cells for regenerative medicine strategies. Endogenous neural precursors within the adult forebrain subependyma can be activated following injury, resulting in their proliferation and migration toward lesion sites where they differentiate into neural cells. The administration of growth factors and immunomodulatory agents following injury augments this activation and has been shown to result in behavioural functional recovery following stroke.Methods and Findings With the goal of enhancing neural precursor migration to facilitate the repair process we report that externally applied direct current electric fields induce rapid and directed cathodal migration of pure populations of undifferentiated adult subependyma-derived neural precursors. Using time-lapse imaging microscopy in vitro we performed an extensive single-cell kinematic analysis demonstrating that this galvanotactic phenomenon is a feature of undifferentiated precursors, and not differentiated phenotypes. Moreover, we have shown that the migratory response of the neural precursors is a direct effect of the electric field and not due to chemotactic gradients. We also identified that epidermal growth factor receptor (EGFR) signaling plays a role in the galvanotactic response as blocking EGFR significantly attenuates the migratory behaviour.ConclusionsThese findings suggest direct current electric fields may be implemented in endogenous repair paradigms to promote migration and tissue repair following neurotrauma.

Highlights

  • Neural precursor cells (NPCs) in the adult brain are promising candidates for the development of strategies to repair central nervous system (CNS) tissue following injury or disease [1]

  • These findings suggest direct current electric fields may be implemented in endogenous repair paradigms to promote migration and tissue repair following neurotrauma

  • Post-imaging immunostaining analysis revealed nestin expression was maintained in the NPCs regardless of the presence or absence of a direct current electric fields (dcEFs) when maintained under growth factor conditions (Figure 1A and 1B)

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Summary

Introduction

Neural precursor cells (NPCs) in the adult brain are promising candidates for the development of strategies to repair central nervous system (CNS) tissue following injury or disease [1]. Following injury several studies have demonstrated the migration of SE-derived NPCs to the site of injury, both in the presence or absence of exogenous factors that activate the cells [2,3,4]. Endogenous neural precursors within the adult forebrain subependyma can be activated following injury, resulting in their proliferation and migration toward lesion sites where they differentiate into neural cells. The administration of growth factors and immunomodulatory agents following injury augments this activation and has been shown to result in behavioural functional recovery following stroke

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