A comprehensive evaluation study of the toxic effects of selected NPs (Ag, ZnO, and CuO) in mesenchymal stem cells (MSCs) that contribute to tissue growth and regeneration in the mouse body will be introduced by RNDr. Michal Šíma, Ph.D. from the Institute of Experimental Medicine of the Czech Academy of Sciences (Department of Nanotoxicology and Molecular Epidemiology) on November 15, 2023 at 2:30 p.m. A ZOOM link will be provided soon.

The effect of metal nanoparticles on gene expression of mouse mesenchymal stem cells

Michal Sima1, Zuzana Simova1, Tereza Cervena1,2, Barbora Echalar1, Zdenek Krejcik2, Jiri Klema3, Vladimir Holan1, Pavel Rossner1

 

1Institute of Experimental Medicine CAS, Department of Nanotoxicology and Molecular Epidemiology, Videnska 1083, 142 20 Prague 4, Czech Republic

2Institute of Experimental Medicine CAS, Department of Genetic Toxicology and Epigenetics, Videnska 1083, 142 20 Prague 4, Czech Republic

3Department of Computer Science, Czech Technical University in Prague, Karlovo namesti 13, 121 35, Prague 2, Czech Republic

Abstract:

Several metal nanoparticles (NPs) are known for their antimicrobial properties. However, they may negatively impact human organism, including mesenchymal stem cells (MSCs), a cell population contributing to tissue growth and regeneration. For the first time, we performed a comprehensive evaluation of the toxic effects of selected NPs (Ag, ZnO, and CuO) in mouse MSCs.

In this project, multiple endpoints such as reactive oxygen species production, lipid peroxidation, DNA alterations, and cell cycle were analyzed. Our results indicated the negative biological impacts of these NPs on MSC. The tested NPs induced intracellular ROS generation, which was most likely partly eliminated by the antioxidant mechanisms, resulting in limited effects on oxidative DNA damage. Furthermore, these NPs affected the G1 and S phases of the cell cycle after 24 h exposure.

We also searched for the changes in mRNA and miRNA expression caused by the exposure of mouse stem cells to the same metal nanoparticles in three various doses. After RNA isolation from cell lysates, mRNA and miRNA libraries were prepared, sequenced, and differential expression was analyzed.

Exposure of MSCs to NPs lead to expression changes most pronounced in case of silver NPs with a stronger effect on mRNA than on miRNA. The weakest reaction was observed after the treatment with zinc oxide NPs. In conclusion, the metal antimicrobial NPs tested in our study exert a negative response in MSC and might not be optimal for combined wound treatment with MSC.

 

Acknowledgements: This work was supported by the Czech Science Foundation (21-17720S).