Adipose-Derived Stem Cell-Derived Extracellular Vesicles Inhibit the Fibrosis of Fibrotic Buccal Mucosal Fibroblasts via the MicroRNA-375/FOXF1 Axis.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Oral submucous fibrosis (OSF) is a precancerous lesion. Adipose-derived stem cell- (ADSC-) derived extracellular vesicles (EVs) (ADSC-EVs) regulate multiple oral diseases. Hence, this study explored the mechanism of ADSC-EVs in OSF. ADSCs were transduced with microRNA- (miR-) 375 mimic. ADSC-EVs and miR-375-overexpressed ADSC-EVs (EVs-miR-375) were extracted and identified. miR-375 expression in EVs and fibrotic buccal mucosal fibroblasts (fBMFs) was detected. EV uptake by fBMFs was observed. The targeted relationship between miR-375 and forkhead box protein F1 (FOXF1) was predicted and verified. After EVs-miR-375 treatment or FOXF1 overexpression, fBMF cell proliferation, migration, invasion, and apoptosis were evaluated, and levels of apoptosis-related proteins (cleaved-caspase-3, Bax, and Bcl-2) and fibrosis markers ( α -SMA, collagen I, and collagen III) were detected. Functional rescue experiments were further performed to verify the role of the miR-375/FOXF1 axis in OSF. miR-375 was notably upregulated in EVs-miR-375 and EVs-miR-375-treated fBMFs (all P < 0.001). ADSC-EVs carried miR-375 into fBMFs. fBMFs can internalize ADSC-EVs. EVs-miR-375 treatment markedly inhibited fBMF cell proliferation, migration, invasion, and fibrosis and promoted apoptosis (all P < 0.01). Moreover, miR-375 targeted FOXF1 in fBMFs. FOXF1 overexpression promoted fBMF cell biological behaviors an

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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