Administration of hypoxic pretreated adipose-derived mesenchymal stem cell exosomes promotes spinal cord repair after injury via delivery of circ-Astn1 and activation of autophagy

被引：0
作者：
Shao, Minghao [1 ,2 ]
Jin, Mingming [3 ]
Lv, Feizhou [1 ]
Ma, Xiaosheng [1 ]
Wei, Zhu [1 ,2 ]
机构：
[1] Fudan Univ, Huashan Hosp, Dept Spine Surg, Shanghai 200040, Peoples R China
[2] Gannan Med Univ, Xingguo Hosp, Dept Spine Surg, 699 Wenming Ave, Ganzhou 342400, Jiangxi, Peoples R China
[3] Shanghai Univ Med & Hlth Sci, Shanghai Key Lab Mol Imaging, Shanghai 201318, Peoples R China
来源：
INTERNATIONAL IMMUNOPHARMACOLOGY | 2025年 / 152卷
基金：
中国国家自然科学基金;
关键词：
Adipose-derived mesenchymal stem cells; Exosome; Spinal cord injury; Circ-Astn1; Microglia autophagy; RECOVERY; ADSCS;
D O I：
10.1016/j.intimp.2025.114324
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
Background: The aim of this study was to investigate the role and mechanism of exosomes isolated from adiposederived mesenchymal stem cells (ADSCs) on spinal cord repair. Methods: High-throughput sequencing was used to investigate abnormal expression of circular RNA (circRNA) in ADSC exosomes pretreated under hypoxic conditions (HExos) and ADSCs exosomes under normal conditions (Exos). The abnormal expression of mRNA in spinal cord tissues was also analyzed using high-throughput sequencing. Bioinformatics and luciferase reporter analyses were used to clarify the relationship among circRNA, micro RNA (miRNA), and mRNA. BV2 cells were used to analyze apoptosis levels and inflammatory cytokine expression under oxygen-glucose deprivation (OGD) conditions by using immunofluorescence and enzyme-linked immunosorbent assay (ELISAs). An SCI mouse model was also constructed and the therapeutic effect of Exos was detected using immunohistochemistry and immunofluorescence. Results: High-throughput sequencing results showed that circ-Astn1 played a role in HExo-mediated spinal cord repair after SCI. Downregulation of circ-Astn1 decreased the therapeutic effect of HExos. We also found that Atg7 played a role in HExo-mediated spinal cord repair after SCI. Luciferase reporter analysis confirmed that both miR-138-5p and Atg7 were downstream targets of circ-Astn1. Downregulation of Atg7 or overexpression of miR138-5p reversed the protective effect of circ-Astn1 on BV2 cells after exposure to OGD conditions. In contrast, upregulation of circ-Astn1 increased the therapeutic effects of Exo-mediated spinal cord repair after SCI via autophagy activation. Conclusions: Taken together, the results indicate that ADSC-Exos containing circ-Astn1 promoted spinal cord repair after SCI by targeting the miR-138-5p/Atg7 pathway, which mediated autophagy.
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页数：11
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