Effect of Electrical Stimulation on Diabetic Human Skin Fibroblast Growth and the Secretion of Cytokines and Growth Factors Involved in Wound Healing

SIMPLE SUMMARY: With the number of diabetic patients on the rise, diabetes has become a major health issue affecting millions of people worldwide. One complication of diabetes is foot ulcers, which are difficult to repair and are thus associated with major clinical problems that may lead to foot amputation and even patient death. The delayed repair of diabetic foot ulcers is due to the slow growth of one of the cell types involved in wound healing, namely, fibroblasts. Fibroblasts inhabit deep skin tissue. Post-wound, they grow and produce skin tissues to enable other cells to close the wound. Even though normal fibroblast growth can be increased by electrical stimulation, it is not clear whether diabetic fibroblast also responds to electrical stimulation. We demonstrated for the first time that a weak direct current electrical field increased diabetic fibroblast growth. The use of electrical stimulation could thus potentially help heal diabetic foot ulcers and ultimately improve patient health and well-being. ABSTRACT: Diabetic foot ulcers are indicative of an impaired wound healing process. This delay may be resolved through electrical stimulation (ES). The goal of the present study was to evaluate the effect of ES on diabetic fibroblast adhesion and growth, and the secretion of cytokines and growth factors. Diabetic human skin fibroblasts (DHSF) were exposed to various intensities of direct current ES (100, 80, 40 and 20 mV/mm). The effect of ES on fibroblast adhesion and growth was evaluated using Hoechst staining, MTT and trypan blue exclusion assays. The secretion of cytokine and growth factor was assessed by cytokine array and ELISA assay. The long-term effects of ES on DHSF shape and growth were determined by optical microscopy and cell count. We demonstrated that ES at 20 and 40 mV/mm promoted cell adhesion, viability and growth. ES also decreased the secretion of pro-inflammatory cytokines IL-6 and IL-8 yet promoted growth factor FGF7 secretion during 48 h post-ES. Finally, the beneficial effect of ES on fibroblast growth was maintained up to 5 days post-ES. Overall results suggest the possible use of low-intensity direct current ES to promote wound healing in diabetic patients.