Electrically stimulated cell migration and its contribution to wound healing

Abstract

Naturally occurring electric fields are known to be morphogenetic cues and associated with growth and healing throughout mammalian and amphibian animals and the plant kingdom. Electricity in animals was discovered in the eighteenth century. Electric fields activate multiple cellular signaling pathways such as PI3K/PTEN, the membrane channel of KCNJ15/Kir4.2 and intracellular polyamines. These pathways are involved in the sensing of physiological electric fields, directional cell migration (galvanotaxis, also known as electrotaxis), and possibly other cellular responses. Importantly, electric fields provide a dominant and over-riding signal that directs cell migration. Electrical stimulation could be a promising therapeutic method in promoting wound healing and activating regeneration of chronic and non-healing wounds. This review provides an update of the physiological role of electric fields, its cellular and molecular mechanisms, its potential therapeutic value, and questions that still await answers.

Keywords: Cell migration; Clinical trials; Electrical stimulation; Endogenous electric fields; Ion transport; Wound healing.

Fig. 1

Formation of endogenous electric potential difference due to ions and charged particles flowing out from the wound edge. Skin and other epithelial layers establish laterally orientated endogenous electric fields that point to the wound center upon being wounded. (Adapted with permission from Song et al. [9] Copyright 2002 by National Academy of Sciences)

Fig. 2

An applied electric field induces polarized activation of PI3K kinase. AKT PH domain-GFP fusion protein reports activation and polarization of PI3K kinase/AKT pathway in an HL-60 differentiated neutrophil-like cell in an electric field. The activation is at the leading edge, when the field polarity is reversed (at 170 s), the new activation site and leading edge form (at 440 s), and the cell moves in the opposite direction. The figure is reproduced with permission from the article of Zhao et al. [26] (Copyright 2006 by Springer Nature)