Engineered exosomes enriched in netrin‑1 modRNA promote axonal growth in spinal cord injury by attenuating inflammation and pyroptosis

Biomaterials Research, 2023 · DOI: https://doi.org/10.1186/s40824-023-00339-0 · Published: January 1, 2023

Spinal Cord Injury Regenerative Medicine Genetics

Simple Explanation

Spinal cord injury (SCI) lacks effective treatments. Exosomes (EX) show promise for SCI treatment because they transport molecules like nucleic acids and proteins. Netrin-1, an axon guidance factor, regulates neuronal growth. The study investigated engineered EX enriched in netrin-1 modified message RNA (modRNA) to treat SCI, aiming to find a novel therapeutic approach. Researchers found that EX-netrin1 regulated inflammation, pyroptosis, and axon growth in SCI via the Unc5b/PI3K/AKT/mTOR pathway, suggesting a new treatment strategy.

Study Duration

Not specified

Participants

48 4-week-old SD female rats

Evidence Level

Not specified

Key Findings

1
EX-netrin1 regulated inflammation, pyroptosis and axon growth in SCI via the Unc5b/PI3K/AKT/mTOR pathway.
2
EX-Netrin1 promoted functional recovery and nerve regeneration and attenuated inflammation and pyroptosis in SCI rats.
3
The therapeutic effect of EX-Netrin1 was diminished by a PI3K inhibitor but reversed by a mTOR agonist

Research Summary

The study explores the therapeutic potential of engineered exosomes (EX) enriched with netrin-1 modRNA in treating spinal cord injury (SCI). In vitro experiments demonstrated that EX-netrin1 attenuated LPS-induced inflammation and pyroptosis, accelerated axonal/dentritic growth, and activated the PI3K/AKT/mTOR signaling pathway. In vivo experiments using a rat model of SCI showed that EX-netrin1 promoted functional recovery, nerve regeneration, and reduced inflammation and pyroptosis.

Practical Implications

Novel therapeutic strategy

The findings suggest a new approach for treating SCI by targeting inflammation, pyroptosis, and axon growth through the Unc5b/PI3K/AKT/mTOR pathway using engineered exosomes.

Potential for clinical translation

The use of MSC-derived exosomes containing netrin-1 modRNA offers a cell-free therapy with improved stability, biocompatibility, and targeted drug delivery for SCI treatment.

Pathway target

The study identifies the Unc5b/PI3K/AKT/mTOR pathway as a critical target for therapeutic intervention in SCI, providing insights for developing more effective treatments.

Study Limitations

1
The study only focused on the Unc5b receptor, ignoring other potential receptors like DCC.
2
Axon growth was only measured macroscopically without microscopic investigation of p-S6, GAP-43, or other molecules.
3
Animal experiments lacked in-depth study of the PI3K/AKT/mTOR axis.

Your Feedback

Was this summary helpful?

Back to Spinal Cord Injury