Epigenetic mechanism of miR-26b-5p-enriched MSCs-EVs attenuates spinal cord injury

Regenerative Therapy, 2024 · DOI: https://doi.org/10.1016/j.reth.2023.10.005 · Published: January 1, 2024

Spinal Cord Injury Regenerative Medicine Genetics

Simple Explanation

This study investigates the therapeutic potential of mesenchymal stem cell-derived extracellular vesicles (MSCs-EVs) enriched with miR-26b-5p in treating spinal cord injury (SCI). The researchers explore how these MSCs-EVs affect inflammation and recovery in SCI. In SCI rat models and PC12 cells, MSCs-EVs were found to deliver miR-26b-5p, which then targeted the KDM6A/NOX4 axis. This targeting reduced inflammation and oxidative stress, promoting recovery from SCI. The study suggests that MSCs-EVs can be a promising therapeutic approach for SCI by modulating the KDM6A/NOX4 axis through miR-26b-5p delivery.

Study Duration

Not specified

Participants

Male adult Sprague Dawley rats (150e200 g)

Evidence Level

Not specified

Key Findings

1
MSCs-EVs alleviate motor dysfunction, inflammation, and oxidative stress in SCI rats, suggesting a therapeutic effect.
2
miR-26b-5p, delivered by MSCs-EVs, inhibits KDM6A, which in turn reduces H3K27me3 at the NOX4 promoter, thus suppressing NOX4 expression.
3
Overexpression of KDM6A or NOX4 reverses the benefits of MSCs-EVs in SCI or LPS-induced cell injury, confirming the KDM6A/NOX4 axis's role.

Research Summary

This study elucidates the mechanism by which MSCs-EVs, enriched with miR-26b-5p, attenuate spinal cord injury (SCI) by targeting the KDM6A/NOX4 axis. The findings indicate that MSCs-EVs deliver miR-26b-5p to inhibit KDM6A, subsequently reducing NOX4 expression and alleviating inflammation and oxidative stress in SCI models. The study provides a rationale for using MSCs-EVs as a therapeutic strategy for SCI, highlighting the role of miR-26b-5p in modulating the KDM6A/NOX4 pathway.

Practical Implications

Therapeutic Strategy

MSCs-EVs enriched with miR-26b-5p could be developed as a therapeutic agent for spinal cord injury.

Targeted Treatment

Targeting the KDM6A/NOX4 axis may provide a novel approach for SCI treatment.

Drug Development

Small molecules or biologics that mimic the action of miR-26b-5p could be designed to inhibit KDM6A and NOX4.

Study Limitations

1
EVs can carry plenty of small molecules and there are also many miRNAs involved in SCI pathology
2
miR-26b-5p has many downstream target genes, but we only veriﬁed the role of the miR-26b-5p/H3K27me3/NOX4 axis in SCI.
3
Our manuscript currently does not explore the differentiation of oligodendrocytes during SCI

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