Extracellular vesicles from TNF-α and TGF-β1-treated ADSCs promote tissue-engineered cartilage regeneration by modulating macrophages via the miR-378a-3p/SIRPα 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)

Background Mesenchymal stem cells (MSCs) possess immunomodulatory properties and are concurrently influenced by the local inflammatory microenvironment. Extracellular vesicles (EVs) derived from MSCs (MSCs-EVs) replicate the therapeutic effects of their parent cells while avoiding the limitations of cell therapy. Elucidating the impact of diverse inflammatory factors on the composition and functionality of MSCs-EVs is crucial for their optimal use, though this remains incompletely understood. The aim of this study was to explore the immunomodulatory effects and underlying mechanisms of EVs derived from adipose-derived stem cells (ADSCs) pretreated with TNF-α and TGF-β1 (α-EVs and β-EVs) on macrophages and tissue-engineered cartilage regeneration. Methods Isolation and identification of EVs from ADSCs cultured in 3D spheres. The effects on chondrocyte and macrophage proliferation, migration, and polarization were evaluated in vitro. In vivo, chondrocytes-laden porous GelMA hydrogel with EVs were implanted into mice to assess chondrocyte regeneration and macrophage infiltration. Small RNA sequencing revealed distinct EVs-miRNA expression profiles, and the target validation confirmed the molecular mechanism. Results In vitro, both α-EVs and β-EVs demonstrated the capacity to modulate macrophage phenotypes. α-EVs more effectively reduced M1 macrophage markers and enhanced M2 polari

Evidence level

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

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