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

Miguel Mateu-Sanz1,2,3, Juan Tornín1,2,3, Bénédicte Brulin4

  • 1Biomaterials, 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.

Cancers
|January 23, 2020
PubMed
Summary

Plasma-activated Ringer's saline (PAR) shows promise for treating osteosarcoma (OS) by selectively killing cancer cells. This innovative therapy utilizes reactive species generated by cold plasma, offering a potential new avenue for difficult-to-treat bone cancers.

Keywords:
Ringer’s salinebone cancercold atmospheric plasmaorganotypic modelosteosarcomaplasma-activated liquidreactive species

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Area of Science:

  • Biomedical Engineering
  • Oncology
  • Plasma Physics

Background:

  • Osteosarcoma (OS) is a primary bone cancer with poor prognosis and challenging treatments.
  • Cold atmospheric plasma (CAP) exhibits anti-cancer properties via reactive oxygen and nitrogen species (RONS).
  • Plasma-activated liquids, particularly saline solutions, have clinical potential but require further investigation for OS therapy.

Purpose of the Study:

  • To investigate the therapeutic potential and mechanisms of plasma-activated Ringer's saline (PAR) against osteosarcoma.
  • To explore the selective cytotoxic effects of PAR on OS cells versus healthy cells.
  • To gain mechanistic insights into PAR's action in both cell cultures and organotypic models.

Main Methods:

  • Cold atmospheric plasma jets were used to generate PAR from Ringer's saline.
  • In vitro studies involved exposing human OS cell lines (SaOS-2, MG-63, U2-OS) and human bone marrow-derived mesenchymal stem cells (hBM-MSCs) to PAR.
  • Organotypic cultures of murine OS were used to validate 2D findings, with histological analysis including Ki-67 staining.

Main Results:

  • PAR demonstrated dose-dependent cytotoxic effects on human OS cells, correlating with increased RONS concentrations.
  • PAR exhibited selectivity, with significant viability maintained in hBM-MSCs under the same treatment conditions.
  • Organotypic cultures confirmed time-dependent cytotoxicity, and histological analysis revealed reduced proliferation (lower Ki-67 expression) in OS tissues.
  • Differential increases in intracellular RONS and DNA damage between OS cells and hBM-MSCs were identified as key mediators of PAR-induced apoptosis.

Conclusions:

  • PAR is a promising therapeutic agent for osteosarcoma, demonstrating selective cancer cell killing.
  • The selectivity and efficacy of PAR are dependent on RONS concentration and the resulting differential cellular responses.
  • PAR warrants further investigation for clinical applications in osteosarcoma treatment, leveraging its ability to induce apoptosis through ROS and DNA damage pathways.