Combined treatment with and weight-supported treadmill training significantly improved motor function in spinal cord injury rats.
Motor function scores in the Exo + TT group were higher than SCI controls from day 7, with significant differences at 4 weeks.
CatWalk analysis indicated better hindlimb coordination and reduced dragging in rats receiving both therapies.
Histological evaluations showed that the combined treatment decreased spinal cord cavitation, inflammation, and fibrosis.
The combination therapy promoted axonal and myelin regeneration, with improved structural organization observed under microscopy.
Western blot analysis revealed decreased expression of fibrosis-related proteins and increased activation of the in the Exo + TT group.
Simplified
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 () 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 XTgait 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 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.
Key numbers
P < 0.05
Score Improvement
Higher scores in the + group from day 7 post-.
P < 0.01
Reduction
Lower expression of , , and α-SMA in + rats.
P < 0.001
Axonal Regeneration
Stronger Tuj1 signal in the + group compared to other groups.
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Declarations. Ethics approval and consent to participate: All animal procedures were performed according to the guidelines of the Institutional Animal Care and Use Committee at Laboratory Animal Center of Nantong University. Project title: Exosomes derived from Menstrual blood-derived mesenchymal stem cells (MenSCs-Exo) and Treadmill Training restore motor function following spinal cord injury. Project number: IACUC20220820-018. Approval date: August 20, 2022. For human Menstrual blood samples, the patients or their guardians provided written informed consent for participation in the study and the use of samples. All the menstrual blood samples’ experiments were carried out according to the guidelines of the Ethics Committee of the Affiliated Nantong Hospital 3 of Nantong University. Study title: MenSCs-Exo loaded GelMA hydrogel promotes functional recovery via miR-421/MAGED1/PI3K-Akt axis. Approval number: EK2023111. Approval date: October 6, 2023. Consent for publication: Not applicable. Competing interests: All authors declare no competing interests.
