Exosomes derived from menstrual blood-derived mesenchymal stem cells and treadmill training restore motor function following SCI by activating PI3K/Akt pathway

作者：Qinghua Wang, Yujing Shi, Liya Zhang, Wenwei Jiang, Yuan-xu Pu, Shiyuan Chen, Hua-qiang Song, Jiaqi Dai, Jiaxi Chen, Jin-yi Liu, Muxing Li, Wenqi Wang, Yuyu Sun, Chuanming Dong, Longju Qi · 发表于：Stem Cell Research & Therapy · 年份：2025 · DOI：10.1186/s13287-025-04794-5 · 被引用次数：3 · 研究领域：Extracellular vesicles in disease、Muscle Physiology and Disorders、Planarian Biology and Electrostimulation

BACKGROUND: Spinal cord injury (SCI) remains a global challenge due to limited neural regeneration and functional recovery. Emerging therapies, such as mesenchymal stem cell-derived exosomes and exercise training, have shown promise, but their individual efficacy is insufficient. The synergistic effects of menstrual blood-derived mesenchymal stem cell-derived exosomes (MenSCs-Exo) and weight-supported treadmill training (WSTT) in SCI repair remain unclear. This study investigated their combined therapeutic potential and underlying mechanisms in SCI rats. METHODS: gait analysis. Histological assessments included hematoxylin and eosin (H&E) staining, Masson's trichrome staining, immunofluorescence for β-tubulin III (Tuj1) and myelin basic protein (MBP), and transmission electron microscopy (TEM). Western blot analyzed fibrosis-related proteins (COL1, COL3, α-SMA) and PI3K/AKT pathway activation (p-AKT, PI3K, β-catenin, LEF1). RESULTS: Combined Exo + TT significantly improved motor function compared to monotherapies. BBB scores in the Exo + TT group were higher than SCI controls from day 7, with marked differences at 4 weeks (P < 0.05). CatWalk analysis revealed enhanced hindlimb coordination, reduced dragging, and improved paw print parameters in Exo + TT rats. Histologically, Exo + TT reduced spinal cord cavitation, inflammation, and fibrosis (P < 0.01 vs. SCI), while promoting axonal (Tuj1) and myelin (MBP) regeneration with ordered structure. TEM showed preserved myelin lame...