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.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Background The aim of this study was to investigate the role and mechanism of exosomes isolated from adipose-derived 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 overexp

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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