Mesenchymal stem cells overexpressing neuropeptide S promote the recovery of rats with spinal cord injury by activating the PI3K/AKT/GSK3β signaling pathway

Stem Cell Research & Therapy, 2025 · DOI: https://doi.org/10.1186/s13287-025-04250-4 · Published: February 20, 2025

Spinal Cord Injury Regenerative Medicine Genetics

Simple Explanation

This study explores a new treatment for spinal cord injury (SCI) using nasal mucosa-derived mesenchymal stem cells (EMSCs) that are modified to produce more of a substance called neuropeptide S (NPS). The goal is to improve cell survival and promote nerve cell growth in the injured area. The modified EMSCs are placed on a hydrogel scaffold and transplanted into rats with complete SCI. The researchers found that these cells survived better, reduced scar formation, and helped regenerate nerve tissue, leading to improved motor function in the rats. The positive effects are believed to be due to the activation of a specific signaling pathway (PI3K/Akt/GSK3β) which promotes the growth and differentiation of nerve cells. This suggests that genetically modifying stem cells could be a promising way to treat SCI in humans.

Study Duration

12 weeks

Participants

72 female Sprague‒Dawley (SD) rats

Evidence Level

Not specified

Key Findings

1
NPS-overexpressing EMSCs showed greater cell survival in the transplanted area compared with stem cells without gene modification within 4 weeks after spinal cord implantation in rats.
2
Stable overexpression of NPS-EMSCs in a rat model with SCI significantly improved the treatment effect, reduced glial scar formation, promoted neural regeneration and endogenous neural stem cell proliferation and differentiation into neurons, and improved motor function.
3
The overexpression of NPS-EMSCs may achieve its effects through the activation of the PI3K/Akt/GSK3β signaling pathway.

Research Summary

This research investigates the therapeutic potential of nasal mucosa-derived mesenchymal stem cells (EMSCs) modified to overexpress neuropeptide S (NPS) for treating spinal cord injury (SCI) in rats. The study demonstrates that transplanting NPS-overexpressing EMSCs, supported by a hydrogel scaffold, enhances cell survival, reduces glial scarring, promotes neural regeneration, and improves motor function in rats with complete SCI. The observed benefits are linked to the activation of the PI3K/Akt/GSK3β signaling pathway, suggesting a mechanism through which NPS-modified EMSCs promote neural stem cell proliferation and differentiation into neurons, offering a promising avenue for clinical applications in SCI treatment.

Practical Implications

Clinical Translation Potential

Gene-modified mesenchymal stem cells show promise for treating spinal cord injuries in humans.

Targeted Therapy Development

The PI3K/Akt/GSK3β signaling pathway is identified as a therapeutic target for promoting neural regeneration.

Hydrogel Scaffold Use

Hydrogels enhance stem cell survival and integration in the injured spinal cord environment.

Study Limitations

1
Challenges in translating the treatment into clinical practice, such as the scalability of EMSC production and safety concerns related to genetic modification.
2
The repair mechanisms of EMSCs in the treatment of SCI were not fully studied. Further research is necessary to better understand the repair mechanisms
3
The cell quality, dose, surgical indications, contraindications, and safety and efficacy evaluation systems in our study were not fully standardized.

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