Nonthermal Plasma Increases Expression of Wound Healing Related Genes in a Keratinocyte Cell Line

Abstract

The application of physical plasma in medicine has great potential in wound healing. Due to the generation of reactive oxygen and nitrogen species (ROS, RNS), emission of UV radiation and the generated electric fields can be used to stimulate epithelial and immune cells. To understand the processes on a molecular level the human keratinocyte cell line HaCaT was treated with a nonthermal atmospheric pressure argon plasma jet (kinpen). Subsequently, cellular RNA was isolated to conduct a quantitative polymerase chain reaction (qPCR) to monitor the magnitude of translation of genes related to wound healing. Plasma treatment induced an upregulation of vascular endothelial growth factor-a (VEGF-A), heparin-binding epidermal growth factor (EGF)-like growth factor (HBEGF), granulocyte macrophage colony-stimulating factor (GM-CSF), prostaglandin-endoperoxide synthase 2 (PTGS2) and interleukin-6 (IL-6) at the mRNA levels. This is a very promising result as the corresponding proteins are likely to be secreted and promote the wound healing process. Therefore plasma potentially induces the secretion of certain cytokines and growth factors, and hence, it could be the stimulus which is necessary to induce chronic wounds to heal.

Non-thermal Plasma Activates Human Keratinocytes by Stimulation of Antioxidant and Phase II Pathways

“…Moreover, apoptotic effects were nearly negligible at all treatment times. In a previous study, it was demonstrated that incubation of cells with plasma-treated medium resulted in an acute death rate under 10% in HaCaT cells (49), which was confirmed by the present data from viability assays. However, the magnitude of apoptosis is strongly dependent on the investigated cell type.…”

“…10D). Interestingly, VEGF expression was indeed shown to be increased by plasma treatment in the cellular environment (49). This growth factor has multiple effector cells among which are keratinocytes and endothelial cells.…”

“…An overexpression of CSF2 suggests beneficial effects in wound healing (e.g. re-epithelialization) via the induction of secondary cytokines and has been shown to improve wound healing by recruitment of leukocytes, enhance keratinocyte proliferation, and increase angiogenesis by VEGF up-regulation (49,84).…”

A cold plasma jet accelerates wound healing in a murine model of full‐thickness skin wounds

“…It signals via RhoA–ROCK and Nod2–NF‐κB signalling pathways and is associated with increased cell motility . We also have previously shown a number of growth factors released by keratinocytes following exposure to plasma‐treated medium, suggesting a possible involvement in enhanced skin cell motility for wound healing …”

Non-thermal plasma treatment induces MAPK signaling in human monocytes

“…Its antibacterial effects are well documented [3,4] and there have been various medical applications such as decontamination of heat sensitive endoscopes and ablation of dental biofilms [5,6]. Preliminary trials showed that plasma application significantly reduced the bacterial load in chronic wounds [7] and potentially stimulated epithelial cells [8,9]. Thus, it seems promising in wound recovery since effective therapies are urgently needed.…”