Adipose-Derived Mesenchymal Stem Cell Exosome miR-146a-5p Attenuates TGF-β2-Induced Transformation of Human Tenon's Capsule Fibroblasts by Targeting SMAD4.

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)

Purpose Conjunctival fibrosis is the major impediment to the success of glaucoma filtration surgery. Exosomes secreted by human adipose-derived mesenchymal stem cells (hADSCs) could alleviate a variety of tissue fibrosis. However, the molecular mechanism of hADSCs-derived exosomes (hADSC-exos) in postoperative glaucoma follicle scarring is still unclear. Methods The hADSC-exos were identified by a transmission electron microscope and nanoparticle tracking analysis. The hADSC-exos were traced in vitro by PKH67 staining, and uptake of exosomes by human Tenon's capsule fibroblast (HTF) cells was detected by the confocal method. After co-culturing hADSC-exos and transforming growth factor beta-2 (TGF-β2), HTF proliferation and migration were detected using Cell Counting Kit-8 and wound healing assay. Protein levels were examined using Western blot. The binding between miR-146a-5p and SMAD4 was predicted and verified using dual-luciferase reporter and RNA immunoprecipitation assay. Gain/loss-of-function studies using microRNA (miRNA)-modified exosomes and direct mimic transfection were performed. Anti-fibrotic efficacy was examined by a trabeculectomy model using New Zealand white rabbits in vivo. Results The hADSC-exos could be internalized by HTFs. The miRNA-146a-5p is the most significantly upregulated in HTFs co-stimulated by TGF-β2 and hADSC-exos. After the screening, miR-146a-

Evidence level

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

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