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Cancers (Basel). 2020 Jan 17;12(1). pii: E227. doi: 10.3390/cancers12010227.

Cold Plasma-Treated Ringer's Saline: A Weapon to Target Osteosarcoma.

Author information

1
Biomaterials, Biomechanics and Tissue Engineering Group, Department Materials Science and Metallurgy, Technical University of Catalonia (UPC), Escola d'Enginyeria Barcelona Est (EEBE), c/Eduard Maristany 14, 08019 Barcelona, Spain.
2
Barcelona Research Center in Multiscale Science and Engineering, UPC, 08019 Barcelona, Spain.
3
Research Centre for Biomedical Engineering (CREB), UPC, 08019 Barcelona, Spain.
4
Inserm, UMR 1238, PHY-OS, Laboratory of Bone Sarcomas and Remodeling of Calcified Tissues, Faculty of Medicine, University of Nantes, 44035 Nantes, France.
5
Institute for Bioengineering of Catalonia (IBEC), Barcelona Institute of Science and Technology (BIST), c/Baldiri i Reixach 10-12, 08028 Barcelona, Spain.

Abstract

Osteosarcoma (OS) is the main primary bone cancer, presenting poor prognosis and difficult treatment. An innovative therapy may be found in cold plasmas, which show anti-cancer effects related to the generation of reactive oxygen and nitrogen species in liquids. In vitro models are based on the effects of plasma-treated culture media on cell cultures. However, effects of plasma-activated saline solutions with clinical application have not yet been explored in OS. The aim of this study is to obtain mechanistic insights on the action of plasma-activated Ringer's saline (PAR) for OS therapy in cell and organotypic cultures. To that aim, cold atmospheric plasma jets were used to obtain PAR, which produced cytotoxic effects in human OS cells (SaOS-2, MG-63, and U2-OS), related to the increasing concentration of reactive oxygen and nitrogen species generated. Proof of selectivity was found in the sustained viability of hBM-MSCs with the same treatments. Organotypic cultures of murine OS confirmed the time-dependent cytotoxicity observed in 2D. Histological analysis showed a decrease in proliferating cells (lower Ki-67 expression). It is shown that the selectivity of PAR is highly dependent on the concentrations of reactive species, being the differential intracellular reactive oxygen species increase and DNA damage between OS cells and hBM-MSCs key mediators for cell apoptosis.

KEYWORDS:

Ringer’s saline; bone cancer; cold atmospheric plasma; organotypic model; osteosarcoma; plasma-activated liquid; reactive species

PMID:
31963398
DOI:
10.3390/cancers12010227
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