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Background <p>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.</p> Methods <p>A T10 spinal cord hemisection model was conducted in adult male Sprague-Dawley rats, which were randomized into five groups: Sham, SCI, Exo (200&#xa0;µg MenSCs-Exo via tail vein injection every 48&#xa0;h for 4 doses), TT (WSTT starting on day 3 post-SCI), and Exo + TT. Motor function was evaluated using the Basso, Beattie, and Bresnahan (BBB) scale and CatWalk XT<sup>®</sup> gait analysis. Histological assessments included hematoxylin and eosin (H&amp;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).</p> Results <p>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 (<i>P</i> &lt; 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 (<i>P</i> &lt; 0.01 vs. SCI), while promoting axonal (Tuj1) and myelin (MBP) regeneration with ordered structure. TEM showed preserved myelin lamellae and reduced axonal degeneration. Western blot confirmed decreased COL1, COL3, and α-SMA expression, along with upregulated p-Akt, PI3K, β-catenin, and LEF1 in Exo + TT rats (<i>P</i> &lt; 0.01).</p> Conclusion <p>MenSCs-Exo combined with WSTT synergistically enhances motor recovery after SCI by promoting tissue repair, reducing fibrosis, and activating the PI3K/Akt pathway. This cell-free therapy paired with rehabilitation exercise offers a novel strategy for SCI treatment.</p> Graphical abstract <p></p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月28日

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  • Qing-hua Wang,
  • Yuan-hu Shi,
  • Li-ya Zhang,
  • Wen-wei Jiang,
  • Yuan-xu Pu,
  • Shi-yuan Chen,
  • Hua-qiang Song,
  • Jia-qi Dai,
  • Jia-xi Chen,
  • Jin-yi Liu,
  • Min-qi Li,
  • Wen-qi Wang,
  • Yu-yu Sun,
  • Chuan-ming Dong,
  • Long-ju Qi

摘要

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

A T10 spinal cord hemisection model was conducted in adult male Sprague-Dawley rats, which were randomized into five groups: Sham, SCI, Exo (200 µg MenSCs-Exo via tail vein injection every 48 h for 4 doses), TT (WSTT starting on day 3 post-SCI), and Exo + TT. Motor function was evaluated using the Basso, Beattie, and Bresnahan (BBB) scale and CatWalk XT® 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 lamellae and reduced axonal degeneration. Western blot confirmed decreased COL1, COL3, and α-SMA expression, along with upregulated p-Akt, PI3K, β-catenin, and LEF1 in Exo + TT rats (P < 0.01).

Conclusion

MenSCs-Exo combined with WSTT synergistically enhances motor recovery after SCI by promoting tissue repair, reducing fibrosis, and activating the PI3K/Akt pathway. This cell-free therapy paired with rehabilitation exercise offers a novel strategy for SCI treatment.

Graphical abstract