# Transcriptomic Profiling of Mouse Mesenchymal Stem Cells Exposed to Metal-Based Nanoparticles

## TL;DR

This study explores how metal-based nanoparticles affect mouse stem cells, revealing both potential healing benefits and possible toxicity.

## Contribution

The study provides novel insights into the transcriptomic and epigenetic effects of Ag, CuO, and ZnO nanoparticles on mouse mesenchymal stem cells.

## Key findings

- All tested metal nanoparticles induced immunomodulatory effects and altered extracellular vesicle production in MSCs.
- Ag nanoparticles caused the most significant changes in gene expression, including those related to oxidative stress and drug metabolism.
- MiR-126 upregulation and MiR-92a downregulation were observed, potentially enhancing MSC healing properties.

## Abstract

Mesenchymal stem cells (MSCs), i.e., adult stem cells with immunomodulatory and secretory properties, contribute to tissue growth and regeneration, including healing processes. Some metal nanoparticles (NPs) are known to exhibit antimicrobial activity and may further potentiate tissue healing. We studied the effect of Ag, CuO, and ZnO NPs after in vitro exposure of mouse MSCs at the transcriptional level in order to reveal the potential toxicity as well as modulation of other processes that may modify the activity of MSCs. mRNA–miRNA interactions were further investigated to explore the epigenetic regulation of gene expression. All the tested NPs mediated immunomodulatory effects on MSCs, generation of extracellular vesicles, inhibition of osteogenesis, and enhancement of adipogenesis. Ag NPs exhibited the most pronounced response; they impacted the expression of the highest number of mRNAs, including those encoding interferon-γ-stimulated genes and genes involved in drug metabolism/cytochrome P450 activity, suggesting a response to the potential toxicity of Ag NPs (oxidative stress). Highly interacting MiR-126 was upregulated by all NPs, while downregulation of MiR-92a was observed after the ZnO NP treatment only, and both effects might be associated with the improvement of MSCs’ healing potency. Overall, our results demonstrate positive effects of NPs on MSCs, although increased oxidative stress caused by Ag NPs may limit the therapeutical potential of the combined MSC+NP treatment.