Electric field stimulation boosts neuronal differentiation of neural stem cells for spinal cord injury treatment via PI3K/Akt/GSK‑3β/β‑catenin activation

Cell & Bioscience, 2023 · DOI: https://doi.org/10.1186/s13578-023-00954-3 · Published: January 3, 2023

Regenerative Medicine Neurology Genetics

Simple Explanation

Neural stem cells (NSCs) are promising for cell replacement therapy in neurological disorders, but they often differentiate into glial cells instead of neurons. This limits their therapeutic potential. Applying a physiological electric field (EF) stimulation can help NSCs differentiate into neurons without the side effects of chemicals, potentially improving neurological recovery after injuries. The study found that EF stimulation boosts neuronal differentiation of NSCs by activating the PI3K/Akt/GSK-3β/β-catenin pathway, improving outcomes in spinal cord injury (SCI) treatment in mice.

Study Duration

7 days (in vitro), up to 56 days (in vivo)

Participants

Mice with spinal cord injury and mouse embryonic neural stem cells (NSCs), human iPSCs

Evidence Level

Not specified

Key Findings

1
Physiological EF stimulation (100 mV/mm) significantly boosts neuronal differentiation of NSCs in vitro, increasing MAP2 positive cells and neuronal process length.
2
EF stimulation activates the PI3K/Akt/GSK-3β/β-catenin signaling cascade in NSCs, and deficiency of either PI3Kγ or β-catenin abolishes the EF-induced neuronal differentiation.
3
Pre-treatment of NSCs with EF stimulation before transplantation into SCI mice improves neurogenesis in the impacted spinal cord and benefits hind limb motor function repair.

Research Summary

This study investigates the effect of physiological electric field (EF) stimulation on neuronal differentiation of neural stem cells (NSCs) for spinal cord injury (SCI) treatment. The results demonstrate that EF stimulation boosts neuronal differentiation of NSCs via the PI3K/Akt/GSK-3β/β-catenin activation, leading to improved neurogenesis and neurofunctional recovery in SCI mice. The findings suggest that pre-treatment with EF stimulation before NSCs transplantation could significantly improve the therapeutic outcome for neurogenesis and neurofunction recovery of SCI.

Practical Implications

Therapeutic Potential

EF stimulation can be used as a non-chemical method to enhance neuronal differentiation of NSCs for cell replacement therapy in neurological disorders.

Clinical Application

Pre-treating NSCs with EF stimulation before transplantation could improve the efficacy of stem cell therapies for SCI and other CNS injuries.

Signaling Pathways

Understanding the PI3K/Akt/GSK-3β/β-catenin signaling pathway in EF-induced neuronal differentiation can lead to the development of targeted therapies.

Study Limitations

1
The study primarily focuses on mouse models, and further research is needed to confirm the results in human clinical trials.
2
The long-term effects of EF-stimulated NSCs transplantation on SCI recovery need to be further investigated.
3
The optimal parameters for EF stimulation (e.g., intensity, duration, frequency) need to be refined for specific neurological conditions.

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