Directed migration of corneal epithelial sheets in physiological electric fields

Area of Science:

• Cell Biology
• Bioelectricity
• Tissue Engineering

Background:

• Endogenous electric fields (EFs) are generated in living tissues, including the cornea.
• Corneal epithelial cell (CEC) sheets play a crucial role in maintaining corneal integrity and wound healing.
• Understanding the influence of environmental cues on cell migration is vital for regenerative medicine.

Purpose of the Study:

• To investigate the effects of small applied electric fields (100-250 mV/mm) on cultured bovine CEC sheets.
• To determine how EFs interact with environmental factors (serum, growth factors) to guide CEC sheet migration.

Main Methods:

• Primary bovine CECs were cultured and exposed to varying EFs in media with or without serum and growth factors.
• Cell sheet migration was tracked and quantified using an image analysis system.
• Specific growth factors investigated included epithelial growth factor, basic fibroblast growth factor, and transforming growth factor-beta 1.

Main Results:

• CEC sheets consistently migrated towards the cathode (negative pole) in a voltage-dependent manner.
• Migration required the presence of serum at low field strengths (up to 200 mV/mm); serum-free conditions showed no migration.
• Growth factors partially restored cathode-directed migration in serum-free medium, and lamellipodia formation was observed at the leading edge.

Conclusions:

• Applied electric fields can effectively direct CEC sheet migration.
• Serum and specific growth factors are essential modulators of EF-directed CEC migration.
• Endogenous EFs in wounded corneas likely interact with environmental cues to promote epithelial sheet migration and wound closure.