DC Electric Fields Induce Rapid Directional Migration in Cultured Human Corneal Epithelial Cells

doi:10.1006/exer.2000.0830

Experimental Eye Research

Volume 70, Issue 5, May 2000, Pages 667-673

https://doi.org/10.1006/exer.2000.0830 Get rights and content

Abstract

After an epithelium is wounded, multiple soluble and extracellular matrix-associated signals induce a repair response. An often-overlooked signal is the endogenous electrical field established in the vicinity of the wound immediately upon disruption of epithelial integrity. Previous studies have detected lateral electric fields of approximately 42 mV mm⁻¹near bovine corneal wounds. In addition, electric fields on the order of 100–200 mV mm⁻¹have been measured lateral to wounds in mammalian epidermis. Here we report the migratory response of human corneal epithelial cells to DC electric fields of similar, physiologic magnitude. Our findings demonstrate that in a 100 mV mm⁻¹DC field, corneal epithelial cells demonstrate directed migration towards the cathode. The migratory speed and distances traversed by cultured human corneal epithelial cells is remarkably similar to those of cultured skin-derived keratinocytes under similar conditions; however, corneal epithelial cells demonstrate a more rapid directional response to the field than keratinocytes. These findings suggest that endogenous, wound-induced electric fields present in the cornea play an important role in human corneal wound healing, by orienting the directional response of migratory cells so that they efficiently re-epithelialize the wounded area.

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Electrical stimulation (ES) has been applied in cell culture system to enhance neural stem cell (NSC) proliferation, neuronal differentiation, migration, and integration. According to the mechanism of its function, ES can be classified into induced electrical (EFs) and electromagnetic fields (EMFs). EFs guide axonal growth and induce directional cell migration, whereas EMFs promote neurogenesis and facilitates NSCs to differentiate into functional neurons. Conductive nanomaterials have been used as functional scaffolds to provide mechanical support and biophysical cues in guiding neural cell growth and differentiation and building complex neural tissue patterns. Nanomaterials may have a combined effect of topographical and electrical cues on NSC migration and differentiation. Electrical cues may promote NSC neurogenesis via specific ion channel activation, such as SCN1α and CACNA1C. To accelerate the future application of ES in preclinical research, we summarized the specific setting, such as current frequency, intensity, and stimulation duration used in various ES devices, as well as the nanomaterials involved, in this review with the possible mechanisms elucidated. This review can be used as a checklist for ES work in stem cell research to enhance the translational process of NSCs in clinical application.
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Electrical stimulation (ES) alone has been shown beneficial for the treatment of wounds and injuries. ES has been shown to aid the re-epithelisation of skin and corneal wounds; to enhance angiogenesis; and to promote the migration of fibroblasts, keratynocytes and epithelial cells [186–192]. ES's ability to induce re-innervation [193,194] and increase skin blood flow [195] aids in the healing of wounds.
Electrical stimulation for delivery of biochemical agents such as genes, proteins and RNA molecules amongst others, holds great potential for controlled therapeutic delivery and in promoting tissue regeneration. Electroactive biomaterials have the capability of delivering these agents in a localized, controlled, responsive and efficient manner. These systems have also been combined for the delivery of both physical and biochemical cues and can be programmed to achieve enhanced effects on healing by establishing control over the microenvironment. This review focuses on current state-of-the-art research in electroactive-based materials towards the delivery of drugs and other therapeutic signalling agents for wound care treatment. Future directions and current challenges for developing effective electroactive approach based therapies for wound care are discussed.
Biomimetic stochastic topography and electric fields synergistically enhance directional migration of corneal epithelial cells in a MMP-3-dependent manner
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Directed migration of corneal epithelial cells (CECs) is critical for maintenance of corneal homeostasis as well as wound healing. Soluble cytoactive factors and the intrinsic chemical attributes of the underlying extracellular matrix (ECM) participate in stimulating and directing migration. The central importance of the intrinsic biophysical attributes of the microenvironment of the cell in modulating an array of fundamental epithelial behaviors including migration has been widely documented. Among the best measures of these attributes are the intrinsic topography and stiffness of the ECM and electric fields (EFs). How cells integrate these multiple simultaneous inputs is not well understood. Here, we present a method that combines the use of (i) topographically patterned substrates (mean pore diameter 800 nm) possessing features that approximate those found in the native corneal basement membrane; and (ii) EFs (0–150 mV mm⁻¹) mimicking those at corneal epithelial wounds that the cells experience in vivo. We found that topographic cues and EFs synergistically regulated directional migration of human CECs and that this was associated with upregulation of matrix metalloproteinase-3 (MMP3). MMP3 expression and activity were significantly elevated with 150 mV mm⁻¹ applied-EF while MMP2/9 remained unaltered. MMP3 expression was elevated in cells cultured on patterned surfaces against planar surfaces. The highest single-cell migration rate was observed with 150 mV mm⁻¹ applied EF on patterned and planar surfaces. When cultured as a confluent sheet, EFs induced collective cell migration on stochastically patterned surfaces compared with dissociated single-cell migration on planar surfaces. These results suggest significant interaction of biophysical cues in regulating cell behaviors and will help define design parameters for corneal prosthetics and help to better understand corneal wound healing.
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^f1: Address correspondence to: Rivkah Isseroff, Department of Dermatology, TB192, University of California, One Shields Avenue, Davis, CA 95616, U.S.A. E-mail: [email protected]

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Regular ArticleDC Electric Fields Induce Rapid Directional Migration in Cultured Human Corneal Epithelial Cells

Abstract

Dev. Biol.

Exper. Eye Res.

J. Invest. Dermatol.

J. Lipid Res.

Exp. Eye Res.

Prog. Neurobiol.

Dev. Biol.

J. Invest. Dermatol.

The glabrous epidermis of cavies contains a powerful battery

Am. J. Physiol.

Electrical and ionic controls of tissue cell locomotion in DC electric fields

J. Neurosci. Res.