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IMSC-derived extracellular vesicles and their miRNA cargo influence inflammation and oxidative damage in an in vitro osteoarthritis model

ABSTRACT: Osteoarthritis is a multifactorial chronic joint disease characterized by progressive cartilage degradation and relevant inflammation. Since there is no effective cure, emerging therapeutic approaches, such as mesenchymal stromal cells (MSCs) transplantation, are currently under investigation. However, the clinical translation of MSC-based therapies is hampered by several limitations, such as donor-dependent variability and heterogeneity related to tissue sources. To address these issues, MSCs derived from induced pluripotent stem cells (iMSCs) have been proposed as a more standardized and scalable alternative. Due to the risks of cell-based therapy, extracellular vesicles (EVs), particularly iMSC-EVs (iEVs), could represent a promising cell-free approach for OA treatment. The present study aimed at characterizing iMSC-derived EVs and evaluating their functional role in modulating inflammatory responses and redox balance in an in vitro OA model. Notably, recent evidence highlights the central role of EV-encapsulated microRNAs (EV-miRNAs) in mediating these effects. Methods EVs isolated from iMSC conditioned media were characterized, and their miRNA content was analyzed at different culture passages. Selected miRNAs were subsequently assessed for their biological activity in an in vitro OA model, with a focus on their impact on inflammatory mediators and oxidative stress parameters. Results Effects of upregulated miRNAs on an in vitro OA model reported a decrease expression levels of pro-inflammatory cytokines. Moreover, the treatment significantly ameliorates ROS accumulation and oxidative damage, restoring antioxidant defenses. Specifically, miRNAs such as hsa-miR-17-5p, has-miR-20a-5p, has-miR-21-5p, has-miR-29a-3p, has-miR-29b-3p, and has-miR-29c-3p differentially reflect the anti-inflammatory and antioxidant effects of iMSCs-EVs treatment, suggesting possible synergistic effects. Discussion These findings support the therapeutic potential of iMSC-derived EVs as a cell-free strategy for OA treatment. The miRNA cargo encapsulated within iEVs appears to play a pivotal role in modulating inflammation and oxidative stress, emphasizing their promise as a novel, minimally invasive approach for disease modification in OA.

ORGANISM(S): Homo sapiens

PROVIDER: GSE309880 | GEO | 2026/09/16

REPOSITORIES: GEO

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IMSC-derived extracellular vesicles and their miRNA cargo influence inflammation and oxidative damage in an in vitro osteoarthritis model

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