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Figure 2. Therapeutic effects of MSC-EVs in liver fibrosis. MSC-EVs from various sources exert multiple therapeutic effects in liver fibrosis by delivering bioactive molecules, including proteins, lipids, and nucleic acids, to liver cells. Key mechanisms include the reversion of HSC activation, mainly through the inhibition of fibrosis-related pathways. MSC-EVs also regulate apoptosis by inducing ferroptosis and lipid peroxidation in HSCs while reducing oxidative stress, necroptosis, and pyroptosis in hepatocytes. Additionally, they promote autophagy, suppress angiogenesis, and modulate immune responses, particularly by driving macrophage polarization toward an anti-inflammatory M2 phenotype. Collectively, these effects contribute to fibrosis attenuation and liver tissue regeneration. Created using BioRender. Chiabotto, G. (2025) https://BioRender.com/aitz8fh. Ang-2: Angiopoietin-2; Beclin-1: autophagy-related protein beclin-1; EMT: epithelial-mesenchymal transition; EVs: extracellular vesicles; HSC: hepatic stellate cell; IFN-γ: interferon-gamma; IkBα: inhibitor of nuclear factor kappa b alpha; IL-4: interleukin-4; IL-6: interleukin-6; IL-10: interleukin-10; IL-13: interleukin-13; Keap1: Kelch-like ECH-associated protein 1; LC3: microtubule-associated protein 1 light chain 3; LPS: lipopolysaccharide; MSC-EVs: mesenchymal stromal cell-derived extracellular vesicles; NF-κB: nuclear factor kappa B; Nrf2: nuclear factor erythroid 2-related factor 2; PI3K/AKT/mTOR: phosphoinositide 3-kinase/protein kinase b/mammalian target of rapamycin; TGF-β: transforming growth factor-beta; TNF-α: tumor necrosis factor-alpha.
