Anti-fibrotic Potential of WJ-MSC Exosomes in Liver Fibrosis: Mechanistic Insights and Dose-Response Efficacy
| Author | Azam Khedri | en |
| Author | Mohammadreza Roshanazadeh | en |
| Author | Mahdi Hatami | en |
| Author | Arash Sanaei | en |
| Author | Sahar Saki | en |
| Author | Samaneh Salehipour Bavarsad | en |
| Orcid | Samaneh Salehipour Bavarsad [0000-0001-7336-2166] | en |
| Issued Date | 2024-12-31 | en |
| Abstract | Background: Hepatic fibrosis is a biological response characterized by the accumulation of extracellular matrix (ECM) during the wound healing process. Hepatic stellate cells (HSCs) play a pivotal role in fibrogenesis, transitioning from quiescent to myofibroblast cell types and leading to excessive ECM production. Platelet-derived growth factor (PDGF), a potent mitogen, is produced by activated HSCs, stimulating cell proliferation and migration. Objectives: This study aims to analyze the impact of Wharton's jelly mesenchymal stem cell (WJ-MSC)-derived exosomes on HSC activation induced by PDGF during liver fibrosis. Methods: Hepatic stellate cells-T6 cells were treated with PDGF-BB for 24 hours to induce activation, followed by treatment with varying concentrations of WJ-MSC-derived exosomes (0, 25, and 50 µg/mL) for another 24 hours. The effects of exosome treatment on HSC activation were evaluated through flow cytometry, differentiation assays, dynamic light scattering (DLS), transmission electron microscopy (TEM), RT-PCR, and western blot analysis. Results: Our study yields promising results, highlighting the potential therapeutic effects of WJ-MSC-derived exosomes on liver fibrosis. The dose-dependent decrease in fibrotic markers such as α-SMA, COLA1, and phosphorylated AKT protein in PDGF-BB-treated HSC-T6 cells suggests that WJ-MSC exosomes exert an anti-fibrotic effect by inhibiting HSC activation. Conclusions: These findings suggest that exosomes derived from WJ-MSCs hold therapeutic promise for liver fibrosis treatment by targeting key pathways involved in HSC activation and fibrogenesis. Further investigation into the underlying mechanisms of this anti-fibrotic effect and the potential clinical applications of WJ-MSC-derived exosomes in liver fibrosis management is warranted. | en |
| DOI | https://doi.org/10.5812/ijpr-149480 | en |
| Keyword | PDGF-BB | en |
| Keyword | p-AKT | en |
| Keyword | WJ-MSCs | en |
| Keyword | Exosome | en |
| Keyword | Liver Fibrosis | en |
| Publisher | Brieflands | en |
| Title | Anti-fibrotic Potential of WJ-MSC Exosomes in Liver Fibrosis: Mechanistic Insights and Dose-Response Efficacy | en |
| Type | Research Article | en |
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