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

Michal Sima1, Helena Libalova1, Zuzana Simova1

  • 1Department of Toxicology and Molecular Epidemiology, Institute of Experimental Medicine of the Czech Academy of Sciences, 14220 Prague, Czech Republic.

International Journal of Molecular Sciences
|August 14, 2025
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Summary

Metal nanoparticles (NPs) modulate mesenchymal stem cells (MSCs) for tissue healing. While Ag, CuO, and ZnO NPs show therapeutic potential, Ag NPs increase oxidative stress, potentially limiting combined treatments.

Keywords:
in vitro exposuremouse mesenchymal stem cellsnanoparticleswhole-genome expression analysis of mRNA and miRNA

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Area of Science:

  • Biomedical Engineering
  • Stem Cell Biology
  • Nanotoxicology

Background:

  • Mesenchymal stem cells (MSCs) are crucial for tissue regeneration due to their immunomodulatory and secretory functions.
  • Metal nanoparticles (NPs) possess antimicrobial properties that may enhance tissue healing.
  • Understanding NP interactions with MSCs is vital for developing effective regenerative therapies.

Purpose of the Study:

  • To investigate the in vitro effects of silver (Ag), copper oxide (CuO), and zinc oxide (ZnO) NPs on mouse MSCs at the transcriptional level.
  • To explore potential toxicity and modulation of MSC activity by these NPs.
  • To examine mRNA-miRNA interactions for insights into epigenetic regulation.

Main Methods:

  • In vitro exposure of mouse MSCs to Ag, CuO, and ZnO NPs.
  • Transcriptional analysis to assess gene expression changes.
  • Investigation of mRNA-miRNA interactions to understand epigenetic regulation.

Main Results:

  • All tested NPs induced immunomodulatory effects, extracellular vesicle generation, inhibited osteogenesis, and enhanced adipogenesis in MSCs.
  • Ag NPs showed the most significant impact, affecting numerous genes, including those related to interferon-γ stimulation and cytochrome P450 activity, indicating potential oxidative stress.
  • MiR-126 was upregulated by all NPs, and MiR-92a was downregulated by ZnO NPs, suggesting a role in enhancing MSC healing potential.

Conclusions:

  • Metal nanoparticles positively modulate mesenchymal stem cells, offering potential for tissue regeneration.
  • Ag NPs may induce oxidative stress, potentially limiting their therapeutic application in combination with MSCs.
  • Further research into NP-MSC interactions is warranted to optimize regenerative strategies.