Guided Migration of Neural Stem Cells Derived from Human Embryonic Stem Cells by an Electric Field

Institute for Regenerative Cures, University of California Davis School of Medicine, California 95817, USA.
Stem Cells (Impact Factor: 6.52). 02/2012; 30(2):349-55. DOI: 10.1002/stem.779
Source: PubMed


Small direct current (DC) electric fields (EFs) guide neurite growth and migration of rodent neural stem cells (NSCs). However, this could be species dependent. Therefore, it is critical to investigate how human NSCs (hNSCs) respond to EF before any possible clinical attempt. Aiming to characterize the EF-stimulated and guided migration of hNSCs, we derived hNSCs from a well-established human embryonic stem cell line H9. Small applied DC EFs, as low as 16 mV/mm, induced significant directional migration toward the cathode. Reversal of the field polarity reversed migration of hNSCs. The galvanotactic/electrotactic response was both time and voltage dependent. The migration directedness and distance to the cathode increased with the increase of field strength. (Rho-kinase) inhibitor Y27632 is used to enhance viability of stem cells and has previously been reported to inhibit EF-guided directional migration in induced pluripotent stem cells and neurons. However, its presence did not significantly affect the directionality of hNSC migration in an EF. Cytokine receptor [C-X-C chemokine receptor type 4 (CXCR4)] is important for chemotaxis of NSCs in the brain. The blockage of CXCR4 did not affect the electrotaxis of hNSCs. We conclude that hNSCs respond to a small EF by directional migration. Applied EFs could potentially be further exploited to guide hNSCs to injured sites in the central nervous system to improve the outcome of various diseases.

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Available from: Xiu-Zhen Zhang, Oct 13, 2014
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    • "The differentiation of cultivated NPCs/NSCs into neurons is also being amplified with exposure to ES (Li et al., 2008; Ariza et al., 2010; Feng et al., 2012; Kobelt et al., 2014). Li et al. (2008) first testified that 68% of the migrating NPCs generate immature neurons under the influence of EFs. "
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    ABSTRACT: Researchers are enthusiastically concerned about neural stem cell (NSC) therapy in a wide array of diseases, including stroke, neurodegenerative disease, spinal cord injury, and depression. Although enormous evidences have demonstrated that neurobehavioral improvement may benefit from NSC-supporting regeneration in animal models, approaches to endogenous and transplanted NSCs are blocked by hurdles of migration, proliferation, maturation, and integration of NSCs. Electrical stimulation (ES) may be a selective non-drug approach for mobilizing NSCs in the central nervous system. This technique is suitable for clinical application, because it is well established and its potential complications are manageable. Here, we provide a comprehensive review of the emerging positive role of different electrical cues in regulating NSC biology in vitro and in vivo, as well as biomaterial-based and chemical stimulation of NSCs. In the future, ES combined with stem cell therapy or other cues probably becomes an approach for promoting brain repair.
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    • "The ROCK inhibitor Y27632 enhanced the viability of stem cells and inhibited EF-guided directional migration in induced pluripotent stem cells and neurons. However, it did not significantly affect the directionality of hNSC migration in an EF (Feng et al., 2012). "
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    • "Furthermore , as part of multidisciplinary approaches to develop the guided migration of stem/progenitor cells strategically, it is potentially beneficial to use EF treatment in combination with stem cell therapy to facilitate neuro-regeneration and repair for a variety of neurodegenerative diseases and CNS injuries. Direct current (DC) electrical field (EF) is an effective cue to guide neurite growth and the migration of neurons and other types of cells (Zhao et al., 2006; Meng et al., 2011; Feng et al., 2012). Unfortunately, the response of ventral midbrain progenitors to an EF cannot be deduced from previous publications, because the guidance effect of EFs for cell migration and neurite growth has significant interspecies difference and is cell type dependent. "
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