Adult Subependymal Neural Precursors, but Not Differentiated Cells, Undergo Rapid Cathodal Migration in the Presence of Direct Current Electric Fields

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.

Multi-Session Transcranial Direct Current Stimulation (tDCS) Elicits Inflammatory and Regenerative Processes in the Rat Brain

“…Several recent reports have demonstrated the direct effect of electric fields on the migration of stem cells in culture. This has been shown in adult mouse NSC from the subventricular zone [19], adult rat NSC from the hippocampus [34], embryonic rat NSC from the lateral ganglionic eminence [20], human embryonic stem (hES) cells and human induced pluripotent stem (hiPS) cells [21], and hES cell-derived NSC [22]. All of those cell types were reported to migrate towards the cathode of the electric field, except the hiPS cells that moved towards the anode [21].…”

A Galvanotaxis Assay for Analysis of Neural Precursor Cell Migration Kinetics in an Externally Applied Direct Current Electric Field

“…Genetic knockout models or siRNA transfection techniques could be used to target genes of interest that may play a role in cell migration or the transduction of a dcEF into cell motility. In our lab, we have modified the galvanotaxis chamber to permit continuous cross-perfusion of fresh culture media within the central trough during experimentation 18 . An appropriate substrate and culture media would need to be selected for other cell types, and the duration of cell seeding prior to imaging should be adjusted as necessary.…”

Novel Stroke Therapeutics: Unraveling Stroke Pathophysiology and Its Impact on Clinical Treatments

“…Increasing the numbers of migrating endogenous stem cells can be achieved using various chemokine receptors such as stromal derived factor1 and integrin β1 (Ohab et al, 2006; Yan et al, 2007), and manipulation of ECM components or electrical fields to guide endogenous NPCs has been investigated (Lee et al, 2006; Babona-Pilipos et al, 2011). However, currently this research has been limited to the preclinical arena.…”