Electrical Stimulation Directs Migration, Enhances and Orients Cell Division and Upregulates the Chemokine Receptors CXCR4 and CXCR2 in Endothelial Cells

Abstract

Natural direct current electric fields (DC EFs) within tissues undergoing angiogenesis have the potential to influence vessel formation, but how they affect endothelial cells is not clear. We therefore quantified behaviours of human umbilical vein endothelial cells (HUVEC) and human microvasculature endothelial cells (HMEC) stimulated by EFsin vitro. Both cell types migrated faster and toward the cathode; HUVECs responded to fields as low as 50mV/mm, but the HMEC threshold was 100 mV/mm. Mitosis was stimulated at 50 mV/mm for HMEC and at 150 mV/mm for HUVECs, but the cleavage plane was oriented orthogonal to the field vector at 200 mV/mm for both cell types. That different field strengths induced different cell responses suggests distinct underlying cellular mechanisms. A physiological electric field also upregulated expression of CXCR4 and CXCR2 chemokine receptors and upregulated phosphorylation of both chemokines in HUVEC and HMEC cells. Evidence that DC EFs direct endothelial cell migration, proliferation and upregulate chemokines involved in wound healing suggests a key role for electrical control of capillary production during healing. Our data contribute to the molecular mechanisms by which DC EFs direct endothelial cell behaviour and present a novel signalling paradigm in wound healing, tissue regeneration and angiogenesis-related diseases.

Electrical stimulation in bone tissue engineering treatments

“…In in vitro 3D-culture studies, Yang et al describes EStim as "promoting synergy" between cells and scaffold material [48]. Finally, it was shown that not only cell alignment, but also cell division plane, could be controlled by externally applied EStim [49,50], theoretically making it possible to control the direction of cellular expansion.…”

Direct Current Electric Field Stimulates Nitric Oxide Production and Promotes NO-Dependent Angiogenesis: Involvement of the PI3K/Akt Signaling Pathway

“…Kanno et al [16] showed that EF-stimulated skeletal muscle cell culture medium augmented the growth of endothelial cells. Cunha et al [36] demonstrated that DC electrical stimulation at 150 mV/ mm and at 300 mV/mm had a promoting effect on the mitosis of HUVECs. Our present study in endothelial cells using 150 mV/mm EF strength stimulation shows that the EF enhances the endothelial cell proliferation rate by approximately 163%, in agreement with these findings.…”

<p>Percutaneous Bioelectric Current Stimulation for Chronic Cluster Headache – A Possible Transformative Approach to Cluster Headache</p>

“…Interestingly electric fields (EF) enhance CXCR2 expression in vascular endothelial cells. 23 Although a number of blood-derived cells show directed cell migration in response to small electrical fields (macrophages, monocytes, neutrophils and T cells 24,25 ), whether mast cells are electrosensitive and might accumulate focally at stimulation sites, is not known but is testable. However, if the EFs established by PBCS needles directed mast cell migration and regulated cytokine secretion and receptor expression as occurs in many other cell types, a mast cell-based explanation of the remarkable efficacy of PBCS in alleviating CH may emerge.…”