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(The FASEB Journal. 2003;17:397-406.)
© 2003 FASEB

Direct visualization of a stratified epithelium reveals that wounds heal by unified sliding of cell sheets

MIN ZHAO12, BING SONG2, JIN PU, JOHN V. FORRESTER* and COLIN D. McCAIG

Departments of Biomedical Sciences and
* Ophthalmology, Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, Scotland, UK

1Correspondence: Department of Biomedical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, Scotland, UK. E-mail: m.zhao{at}abdn.ac.uk or c.mccaig{at}abdn.ac.uk

Observing cells in their original niche is a key link between the information gleaned from planar culture and in vivo physiology and pathology. A new approach combining the transparency of the cornea, Hoffman modulation optics, and digital imaging allowed movements of individual corneal cells to be viewed directly in situ. 3-Dimensional time-lapse movies imaging unstained cells within the stratified corneal epithelium during wound healing were made. Tracking cell movements dynamically provided a definitive answer to the long-standing question: does a stratified epithelium heal by "sliding" of cell sheets as a coherent unit or do individual cells "leap frog" each other at the wound margin? A wound in the corneal epithelium healed primarily by sliding of the whole epithelium, with ~95% of cells moving with similar speed and trajectories and with little change in their relative position. Only 5% of cells changed layers, with equal proportions moving up or down. Epithelial healing in situ occurred in three phases: a latency, migration, and reconstruction phase. This model provides a unique system to study the behaviors of individual cells in their original niche. It shows that cells slide into a wound as a unified unit to heal a stratified epithelium.—Zhao, M., Song, B., Pu, J., Forrester, J. V., McCaig, C. D. Direct visualization of a stratified epithelium reveals that wounds heal by unified sliding of cell sheets.


Key Words: wound healing • stratified epithelium • corneal epithelium • corneal organ culture • cell migration




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