Temporal dynamics of ADSC therapy in skin fibrosis: unraveling the roles of ROS/NF-κB/TSG-6 signaling 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 Cutaneous fibrosis, particularly in localized scleroderma (LoS), poses a considerable therapeutic challenge owing to its progressive characteristics and the subsequent effects on quality of life. Although ADSCs exhibit therapeutic potential for fibrosis, their spatiotemporal mechanisms of action, particularly within fibrotic microenvironments, remain poorly characterized. This study sought to clarify the spatiotemporal dynamics and molecular mechanisms of ADSC-mediated fibrosis resolution in bleomycin (BLM)-induced murine LoS model. Methods Skin fibrosis was induced in C57BL/6J mice through daily subcutaneous injections of bleomycin (BLM) administered over a period of four weeks. GFP-labeled mouse or human ADSCs were injected into the fibrotic dorsum. ADSC distribution was tracked using fluorescence imaging and flow cytometry. Skin fibrosis was assessed histologically (H&E, Masson's trichrome, α-SMA, COL1) and molecularly (qRT-PCR for cytokines). Transcriptomic profiling (RNA-seq) of sorted GFP + ADSCs was performed on days 1, 7, and 14 post-injection. Key pathways (ROS, NF-κB, TSG-6) were validated in vitro using ADSCs and human LoS-derived fibroblasts (LoSFs) via pharmacological inhibition, gene knockdown (shTSG-6), co-culture, Western blotting, and dual-luciferase assays. Results ADSCs mitigated dermal thickening, collagen deposition, α-SMA expression, and inflamm

Evidence level

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

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