Umbilical mesenchymal stem cell-derived exosomes promote spinal cord functional recovery through the miR-146b/TLR4 -mediated NF-κB p65 signaling pathway in rats

Biochemistry and Biophysics Reports, 2023 · DOI: https://doi.org/10.1016/j.bbrep.2023.101497 · Published: June 5, 2023

Spinal Cord Injury Regenerative Medicine Genetics

Simple Explanation

Spinal cord injury (SCI) is a severe condition with limited effective treatments. This study investigates the potential of exosomes derived from mesenchymal stem cells (MSCs) to aid in SCI recovery. The researchers used exosomes extracted from human umbilical cord mesenchymal stem cells (hUCMSCs) and tested their effects on a rat SCI model and a cell model. The study found that these exosomes, particularly those containing miR-146b, can help protect neurons from spinal cord injury by targeting TLR4 and inactivating the NF-κB signaling pathway.

Study Duration

14 days

Participants

Male (Sprague-Dawley) SD rats (8-weeks old)

Evidence Level

Not specified

Key Findings

1
hUCMSC-derived exosomes notably alleviate spinal cord injury and cell apoptosis in a rat model.
2
Exosomal miR-146b treatment suppresses the release of inflammatory cytokines such as IL-1β, IL-6, and TNFα.
3
MiR-146b directly interacts with the 3′-untranslated region (3′UTR) of TLR4, suppressing its expression and inactivating the NF-κB signaling pathway.

Research Summary

This study investigates the therapeutic potential of human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSCs) containing miR-146b for spinal cord injury (SCI) treatment. The findings demonstrate that hUCMSC-derived exosomes, particularly exosomal miR-146b, can alleviate SCI-induced spinal cord injury and reduce the production of inflammation cytokines. The mechanism involves miR-146b targeting Toll-like receptor 4 (TLR4) to suppress the NF-κB pathway, ultimately protecting neurons from SCI.

Practical Implications

Therapeutic Development

hUCMSCs-derived exosomal miR-146b offers a potential therapeutic strategy for spinal cord injury.

Targeted Therapy

Targeting the TLR4/NF-κB pathway with miR-146b could be a key approach to reduce inflammation and promote neuron protection in SCI.

Exosome Delivery

Utilizing exosomes as a delivery system for miR-146b provides a novel method for SCI repairment.

Study Limitations

1
The study primarily uses a rat SCI model and LPS-stimulated PC12 cells, which may not fully replicate the complexity of human SCI.
2
The precise effects of miR-146b produced by different cells in the brain (neurons, microglia, astrocytes) and its impact on primary cells remain unknown.
3
Further research is needed to explore the detailed effects of miR-146b on the neuron system during SCI.

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