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. 2025 Aug 5;26(15):7583.
doi: 10.3390/ijms26157583.

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

Michal Sima  1 , Helena Libalova  1 , Zuzana Simova  1 , Barbora Echalar  1 , Katerina Palacka  1 , Tereza Cervena  1 , Jiri Klema  2 , Zdenek Krejcik  1 , Vladimir Holan  1 , Pavel Rossner  1
Affiliations

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

Michal Sima et al. Int J Mol Sci. .

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.

Keywords: in vitro exposure; mouse mesenchymal stem cells; nanoparticles; whole-genome expression analysis of mRNA and miRNA.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
The distribution of common and unique DEGs after exposure of MSCs to three different doses (L—low; M—medium; H—high) of three nanomaterials (Ag, CuO, and ZnO NPs).
Figure 2
Figure 2
Numbers of affected biological pathways after exposure of MSCs to three different doses (L—low; M—medium; H—high) of three nanomaterials (Ag, CuO, and ZnO NPs). Ten pathways found in more than one comparison are shown by name.
Figure 3
Figure 3
The distribution of common and unique DEmiRNAs after exposure of MSCs to three different doses (L—low; M—medium; H—high) of nanomaterials (Ag, CuO, and ZnO NPs).
Figure 4
Figure 4
Plots showing the top 50 significant interactions of DEmiRNAs-DEGs after the exposure of MSCs to three nanomaterials (Ag, CuO, and ZnO NPs). Blue and red color of the nodes indicates RNA upregulation and downregulation, respectively. The size of the nodes represents the strength of deregulation (log2fold change).
Figure 4
Figure 4
Plots showing the top 50 significant interactions of DEmiRNAs-DEGs after the exposure of MSCs to three nanomaterials (Ag, CuO, and ZnO NPs). Blue and red color of the nodes indicates RNA upregulation and downregulation, respectively. The size of the nodes represents the strength of deregulation (log2fold change).
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