4.5 Article

Bioelectric Signaling: Role of Bioelectricity in Directional Cell Migration in Wound Healing

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COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/cshperspect.a041236

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资金

  1. Defense Advanced Research Projects Agency (DARPA) [D20AC00003]
  2. Air Force Office of Scientific Research (AFOSR) Multidisciplinary Research Program of the University Research Initiative (MURI) grant [FA9550-16-1-0052]
  3. National Institutes of Health (NIH) [1R01EY019101]
  4. National Eye Institute (NEI) Core Grant [P-30 EY012576]
  5. Research to Prevent Blindness, Inc.
  6. Program Leader: Marco Rolandi, University of California Santa Cruz)

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Understanding and utilizing wound bioelectrical signaling is crucial for wound healing and regeneration, as the electric fields generated during wound formation play a significant role in directing the migration of epithelial cells.
In wound healing, individual cells' behaviors coordinate movement toward the wound center to restore small or large barrier defects. The migration of epithelial cells as a continuous sheet structure is one of the most important processes by which the skin barrier is restored. How such multicellular and tissue level movement is initiated upon injury, coordinated during healing, and stopped when wounds healed has been a research focus for decades. When skin is wounded, the compromised epithelial barrier generates endogenous electric fields (EFs), produced by ion channels and maintained by cell junctions. These EFs are present across wounds, with the cathodal pole at the wound center. Epithelial cells detect minute EFs and migrate directionally in response to electrical signals. It has long been postulated that the naturally occurring EFs facilitate wound healing by guiding cell migration. It is not until recently that experimental evidence has shown that large epithelial sheets of keratinocytes or corneal epithelial cells respond to applied EFs by collective directional migration. Although some of the mechanisms of the collective cell migration are similar to those used by isolated cells, there are unique mechanisms that govern the coordinated movement of the cohesive sheet. We will review the understanding of wound EFs and how epithelial cells and other cells important to wound healing respond to the electric signals individually as well as collectively. Mounting evidence suggests that wound bioelectrical signaling is an important mechanism in healing. Critical understanding and proper exploitation of this mechanism will be important for better wound healing and regeneration.

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