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Extracellular Vesicles from Mesenchymal Stem Cells Alleviate Spinal Cord Injury via the miR-486-5p/PTEN/PI3K/AKT
Yuhong Chen1, Jinghui Zhu2,3, Xiujuan Wang4
1The Fifth Central Hospital of Tianjin. No. 41 Zhejiang Road, Binhai New Area, Tianjin, 300450, China.
Introduction:
Spinal Cord Injury (SCI) is a severe central nervous system disorder with limited effective treatments. Mesenchymal stem cell (MSC)-derived exosomes have emerged as important mediators of intercellular communication and carry microRNAs with potential neuroprotective properties. This study aimed to explore the role and underlying mechanism of human umbilical cord MSC (hUMSC)-derived exosomal miR-486-5p in experimental SCI.
Methods:
Exosomes were isolated from hUMSCs and characterized by transmission electron microscopy, nanoparticle tracking analysis, and exosomal marker expression. A rat SCI model and an LPS-induced PC12 cell inflammatory injury model were established. Histological injury and apoptosis were assessed by HE staining and TUNEL assay. Inflammatory cytokine levels were measured by ELISA. Cell viability, apoptosis, and gene and protein expression were evaluated using CCK-8 assay, flow cytometry, qPCR, and western blotting. A dual-luciferase reporter assay was performed to validate the interaction between miR-486-5p and PTEN.
Results:
hUMSC-derived exosomes attenuated spinal cord tissue damage, reduced neuronal apoptosis, and suppressed inflammatory cytokine production in vivo and in vitro. Inhibition of exosomal miR-486-5p partially reversed these protective effects. Mechanistically, miR-486-5p directly targeted the 3'-UTR of PTEN, leading to reduced PTEN expression and enhanced phosphorylation of AKT and mTOR.
Discussion:
These findings indicate that exosomal miR-486-5p contributes to the regulation of apoptosis- and inflammation-associated molecular events following SCI, primarily through modulation of the PTEN/AKT/mTOR signaling pathway. Given the experimental design, these results should be interpreted as mechanistic insights rather than evidence of functional recovery.
Conclusion:
hUMSC-derived exosomal miR-486-5p alleviates apoptosis and inflammation following SCI by targeting PTEN and activating the AKT/mTOR pathway. These findings provide mechanistic support for the potential application of exosome-based miRNA therapy in SCI.
