No abstract

Non-thermal atmospheric pressure plasma has recently gained attention in the field of biomedical and clinical applications. In the area of plasma medicine research, one promising approach is to promote wound healing by stimulation of cells involved. To understand basic molecular and cellular mechanisms triggered by plasma treatment, we investigated biological effects of an argon plasma jet kinpen on human epithelial skin cells. For assessment of transcriptome changes cell culture medium was plasma treated and applied to the HaCaT keratinocyte cell culture (indirect treatment). Consequently, whole-genome microarrays were used to analyze this interaction in detail and identified a statistically significant modification of 3,274 genes including 1,828 up- and 1,446 downregulated genes. Particularly, cells after indirect plasma treatment are characterized by differential expression of a considerable number of genes involved in the response to stress. In this regard, we found a plasma-dependent regulation of oxidative stress answer and increased expression of enzymes of the antioxidative defense system (e.g. 91 oxidoreductases). Our results demonstrate that plasma not only induces cell reactions of stress-sensing but also of proliferative nature. Consistent with gene expression changes as well as Ingenuity Pathway Analysis prediction, we propose that stimulating doses of plasma may protect epithelial skin cells in wound healing by promoting proliferation and differentiation. In conclusion, gene expression profiling may become an important tool in identifying plasma-related changes of gene expression. Our results underline the enormous clinical potential of plasma as a biomedical tool for stimulation of epithelial skin cells.

Cold plasma has become a promising application in the fields of biology and medicine. Its anti‐microbial effects and stimulating properties on eukaryotic cells make plasma an encouraging option in treatment of chronic wounds. Apart from fibroblasts or keratinocytes, immune cells have a major contribution in wound healing. In this study, human peripheral blood mononuclear cells (PBMC) were tested for viability and proliferation after treatment with an atmospheric pressure argon plasma jet. In a treatment time dependent manner compromised viability of PBMC and proliferation of T cells could be shown and was assigned to induced apoptosis. Negligible cell damage was observed after short plasma exposure. Finally, plasma did not cause loss of function and treated but viable T cells retained the ability to proliferate.

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 application has become a promising field of investigation in chronic wound healing research over the past few decades. In addition to its well-characterized antibacterial effects, plasma potentially promotes the growth of eukaryotic cells. To date, mainly epithelial skin cells have been examined regarding the impact of plasma treatment on chronic wound healing. However, immune cells also are involved in wound healing as well as the removal of pathogens. Therefore, we compared the survival behavior of 2 human leukocyte cell lines (a monocyte and a CD4 + T helper cell line) and their respective human blood counterparts after exposure to plasma. Measurements of early and late apoptotic cells demonstrate that freshly isolated blood cells were more susceptible to apoptosis induction than the cell lines. Furthermore, blood and cell line monocytes tolerated longer plasma exposure compared with blood and cell line CD4 + T helper cells.