Hypoxia-treated umbilical mesenchymal stem cell alleviates spinal cord ischemia-reperfusion injury in SCI by circular RNA circOXNAD1/ miR-29a-3p/ FOXO3a axis

Biochemistry and Biophysics Reports, 2023 · DOI: https://doi.org/10.1016/j.bbrep.2023.101458 · Published: March 13, 2023

Spinal Cord Injury Genetics

Simple Explanation

Spinal cord injuries can lead to neural dysfunction and paralysis. Mesenchymal stem cells (MSCs) are being studied for disease treatment. This study focuses on the potential of a specific circular RNA, circOXNAD1, from human umbilical cord MSCs (HucMSCs) to help with spinal cord injuries. Researchers used a rat model of spinal cord injury and treated it with exosomes from HucMSCs that had been exposed to low oxygen conditions (hypoxia). The results showed that this treatment reduced spinal cord tissue damage, improved limb function, and lowered inflammation. The study also found that circOXNAD1 interacts with miR-29a-3p, which in turn affects FOXO3a, a protein involved in cell processes. By manipulating these interactions, the researchers were able to reverse the effects of circOXNAD1 depletion, suggesting a key role for this pathway in the observed benefits.

Study Duration

Not specified

Participants

Male SD rats that aged 8-weeks old and weighed around 200 g

Evidence Level

In vivo rat spinal cord injury (SCI) model and In vitro hypoxia and reoxygenation (H/R) model

Key Findings

1
Hypoxia-HucMSCs-derived exosomal circOXNAD1 alleviated the spinal cord tissue injury in SCI, improved limb motor function, decreased production of inflammatory factors
2
Hypoxia-HucMSCs-derived exosomal circOXNAD1 improved neuron proliferation and alleviated apoptosis.
3
circOXNAD1 directly interact with miR-29a-3p and miR-29a-3p targets the 3′UTR of FOXO3a in neurons.

Research Summary

This study investigates the therapeutic potential of hypoxia-induced exosomal circular RNA OXNAD1 from human umbilical cord mesenchymal stem cells (HucMSCs) against spinal cord ischemia reperfusion (SCIR). The results showed that Hypoxia-HucMSCs-derived exosomal circOXNAD1 alleviated the spinal cord tissue injury in SCI, improved limb motor function, decreased production of inflammatory factors. Mechanistically, circOXNAD1 directly interact with miR-29a-3p and miR-29a-3p targets the 3′UTR of FOXO3a in neurons. This work provides novel evidence for MSC-derived exosomal circOXNAD1 in the treatment of SCI.

Practical Implications

Therapeutic Potential

MSC-derived exosomal circOXNAD1 could be a novel therapeutic target for spinal cord injury.

Drug Development

Targeting the circOXNAD1/miR-29a-3p/FOXO3a axis may lead to new drug development strategies for SCI treatment.

Cell-Free Therapy

Hypoxia-stimulated MSCs secret a different spectrum of signaling factors that may facilitate the therapy of diseases

Study Limitations

1
Further research is needed to understand the long-term effects of circOXNAD1 treatment.
2
The study focuses on a specific circRNA; other factors may also contribute to the therapeutic effects of MSC exosomes.
3
The precise mechanisms by which FOXO3a influences neuroprotection need further investigation.

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