DC Electric Fields Induce Distinct Preangiogenic Responses in Microvascular and Macrovascular Cells

Abstract

Objective— Electrical stimulation induces significant angiogenesis in vivo. We have shown recently that electrical stimulation induces directional migration, reorientation, and elongation of macrovascular endothelial cells. Because angiogenesis occurs mainly in the microvasculature, we have extended this observation to include human microvascular endothelial cells (HMEC-1s) and compared the responses with that of vascular fibroblasts and smooth muscle cells and human umbilical vein endothelial cells. Methods and Results— Four types of vascular cells were cultured in electric fields (EFs). Dynamic cell behaviors were recorded and analyzed with an image analyzer. EFs of 150 to 400 mV/mm induced directed migration, reorientation, and elongation of all the vascular cells. HMEC-1s showed the greatest directional migration (migration rate of 11 μm/h and directedness of 0.35 at 200 mV/mm). Most intriguingly, HMEC-1s migrated toward the cathode, whereas the other cell types migrated toward the anode. Conclusions— Endothelial cells derived from angiogenic microvascular as opposed to nonangiogenic macrovascular tissues were more responsive to electrical stimulation. This intriguing directional selectivity indicates that a DC electrical signal as a directional cue may be able to play a role in the spatial organization of vascular structure.