hUC-MSCs and derived exosomes attenuate DEX-induced muscle atrophy through modulation of estrogen signaling pathway

作者：Na Li, Xiaoqin Liu, Qiong Wang, Yushu Chen, Chao Han, Chao Qu, Xin Guan, Wei Zou, Xiaomin Wang, Ang Li, Yin Zhang, Liping Zhu, Ruifeng Du, Jing Liu, Yanfu Wang · 发表于：Stem Cell Research & Therapy · 年份：2025 · DOI：10.1186/s13287-025-04328-z · 被引用次数：8 · 研究领域：Muscle Physiology and Disorders、Extracellular vesicles in disease、Mesenchymal stem cell research

BACKGROUND: Sarcopenia, a multifactorial syndrome characterized by progressive loss of skeletal muscle mass and strength, combined with impaired physical function, is associated primarily with aging but also driven by chronic inflammation, immobility, and endocrine dysregulation. It leads to increased risks of frailty, falls, and loss of independence, posing a major public health challenge for aging populations. Although human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) and their derived exosomes (MSC-Exos) have demonstrated remarkable potential in regenerative medicine, their safety and efficacy in treating sarcopenia remain unclear. To address this issue, we conducted a preclinical study to systematically evaluate their therapeutic potential and safety. METHODS: Male C57BL/6 J mice were treated with dexamethasone (20 mg/kg, i.p.) to induce muscle atrophy. Subsequently, bilateral intramuscular injection of hUC-MSCs (1 × 10⁶ cells/kg), exosomes (100 μg), or intraperitoneal injected of SNG162 (40 mg/kg) for two weeks. Gastrocnemius muscles were excised for histological analysis, TUNEL staining, Western blotting, RNA sequencing, and qPCR. Differentiated C2C12 myotubes were treated with 10 μM dexamethasone and co-cultured with hUC-MSCs or exosomes for 24 h. Samples were collected for qPCR, Western blot analyses and flow cytometry. EdU labeling was used to assess cell proliferation, MyHC and MDC immunofluorescence staining were employed to assess myotube morphology a...