title: Guided migration of neural stem cells derived from human embryonic stem cells by an electric field.
abstract: 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.
authors.affiliation: Institute for Regenerative Cures, University of California Davis School of Medicine, California 95817, USA.
authors.forename: Jun-Feng
authors.initials: JF
authors.lastname: Feng
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.forename: Xiu-Zhen
authors.initials: XZ
authors.lastname: Zhang
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Ji-Yao
authors.initials: JY
authors.lastname: Jiang
authors.forename: Jan
authors.initials: J
authors.lastname: Nolta
authors.forename: Min
authors.initials: M
authors.lastname: Zhao
mesh_terms: D000577:Amides / Q000494:pharmacology; D001596:Benzylamines; D002465:Cell Movement; D002478:Cells, Cultured; D000080027:Cyclams; D004560:Electricity; D053595:Embryonic Stem Cells / Q000502:physiology*; D048091:Guided Tissue Regeneration; D006571:Heterocyclic Compounds / Q000494:pharmacology; D006801:Humans; D009416:Nerve Regeneration; D058953:Neural Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000378:metabolism; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000577:Amides; D001596:Benzylamines; C527276:CXCR4 protein, human; D000080027:Cyclams; D006571:Heterocyclic Compounds; D011725:Pyridines; D019718:Receptors, CXCR4; C108830:Y 27632; D054460:rho-Associated Kinases; C088327:plerixafor
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