Dose-Dependent Effects of Cold Atmospheric Argon Plasma on the Mesenchymal Stem and Osteosarcoma Cells In Vitro

Abstract

The antimicrobial, anti-inflammatory and tissue-stimulating effects of cold argon atmospheric plasma (CAAP) accelerate its use in various fields of medicine. Here, we investigated the effects of CAAP at different radiation doses on mesenchymal stem cells (MSCs) and human osteosarcoma (MNNG/HOS) cells. We observed an increase in the growth rate of MSCs at sufficiently low irradiation doses (10–15 min) of CAAP, while the growth of MNNG/HOS cells was slowed down to 41% at the same irradiation doses. Using flow cytometry, we found that these effects are associated with cell cycle arrest and extended death of cancer cells by necrosis. Reactive oxygen species (ROS) formation was detected in both types of cells after 15 min of CAAP treatment. Evaluation of the genes’ transcriptional activity showed that exposure to low doses of CAAP activates the expression of genes responsible for proliferation, DNA replication, and transition between phases of the cell cycle in MSCs. There was a decrease in the transcriptional activity of most of the studied genes in MNNG/HOS osteosarcoma cancer cells. However, increased transcription of osteogenic differentiation genes was observed in normal and cancer cells. The selective effects of low and high doses of CAAP treatment on cancer and normal cells that we found can be considered in terms of hormesis. The low dose of cold argon plasma irradiation stimulated the vital processes in stem cells due to the slight generation of reactive oxygen species. In cancer cells, the same doses evidently lead to the formation of oxidative stress, which was accompanied by a proliferation inhibition and cell death. The differences in the cancer and normal cells’ responses are probably due to different sensitivity to exogenous oxidative stress. Such a selective effect of CAAP action can be used in the combined therapy of oncological diseases such as skin neoplasms, or for the removal of remaining cancer cells after surgical removal of a tumor.

Ceramic‐hydrogel composite as carrier for cold‐plasma reactive‐species: Safety and osteogenic capacity in vivo

“…Interestingly, the cytotoxic effects of plasma‐treated Gel/Alg only affected cancer cells, since the viability of hMSC was not affected (Figure 3d). This selectivity is in agreement with previous works dealing with PTLs in different cancer types [ 33,56–58 ] while being the first to report this action from a Gel/Alg hydrogel. The suggested mechanism behind the selectivity of plasma is based on the higher metabolic levels and basal intracellular ROS levels in cancer cells versus nonmalignant cells.…”

Periodic Exposure of Plasma-Activated Medium Alters Fibroblast Cellular Homoeostasis

“…Changes in antioxidant systems coordinate and regulate the flux of energy metabolic pathways [ 46 ]. Low doses of reactive species can stimulate cellular proliferation by enhancing energy output, while high doses of reactive species can inhibit proliferation by affecting cellular and mitochondrial energetics [ 43 , 47 , 48 ]. As described previously, 25% and 50% PAM exposure did not reduce ATP levels in fibroblasts, while 100% PAM decreased the ATP levels significantly ( Figure 4 A and Figure S4 ).…”

Influence of Redox Stress on Crosstalk between Fibroblasts and Keratinocytes

“…ATP synthesis and cellular health are largely dependent on the structural integrity and function of mitochondria. Exposure to low doses of oxidative stress can stimulate non-malignant cell proliferation, while high doses may inhibit cellular metabolism and eventually proliferation [ 47 , 48 , 49 , 50 , 51 ]. This was expected as non-malignant cells are assumed to have a high tolerance towards redox stress with a low death rate compared with malignant cells.…”