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  4. Combination of epidural electrical stimulation with ex vivo triple gene therapy for spinal cord injury: a proof of principle study

Combination of epidural electrical stimulation with ex vivo triple gene therapy for spinal cord injury: a proof of principle study

Neural Regen Res, 2021 · DOI: https://doi.org/10.4103/1673-5374.293150 · Published: September 22, 2020

Spinal Cord InjuryGeneticsNeurorehabilitation

Simple Explanation

This study explores combining epidural electrical stimulation (EES) with gene therapy to treat spinal cord injury (SCI) in rats. The gene therapy involves transplanting genetically modified human umbilical cord blood cells (UCBMCs) to produce therapeutic molecules. Rats with SCI received intrathecal infusions of UCBMCs expressing genes for VEGF, GDNF, and NCAM, followed by EES at specific spinal cord locations. The combined treatment showed improvements in knee joint function and muscle fiber preservation. The study found reduced apoptosis and increased preservation of gray and white matter in rats treated with the combined therapy. This suggests the combined approach may enhance nerve cell survival and regeneration after SCI.

Study Duration
30 days
Participants
Female Wistar rats (7 months old, 250–300 g)
Evidence Level
Not specified

Key Findings

  • 1
    Rats subjected to the combined treatment showed a limited functional improvement of the knee joint and high preservation of muscle fiber area.
  • 2
    Beneficial cellular outcomes such as reduced apoptosis and increased sparing of the gray and white matters were found in rats subjected to the combined epidural electrical stimulation with gene therapy.
  • 3
    The study presents the first proof of principle study of combination of the multisite epidural electrical stimulation with ex vivo triple gene therapy (VEGF, GDNF and NCAM) for treatment of spinal cord injury in rat models.

Research Summary

This study investigates the combination of epidural electrical stimulation (EES) with ex vivo triple gene therapy for spinal cord injury (SCI) in rat models. The gene therapy involves transplanting genetically engineered human umbilical cord blood mononuclear cells (UCBMCs) expressing VEGF, GDNF, and NCAM. The results showed that rats receiving the combined treatment exhibited improved knee joint function, muscle fiber preservation, reduced apoptosis, and increased sparing of gray and white matter compared to the control group. The findings suggest that the combined approach of EES and triple gene therapy has a synergistic effect on promoting morpho-functional recovery after SCI in rats, offering a potential therapeutic strategy for SCI treatment.

Practical Implications

Potential therapeutic strategy

The combination of EES and gene therapy may offer a novel approach to treat SCI.

Clinical translation

Further research is needed to optimize the EES protocol for SCI patients undergoing gene therapy.

Further investigation

The beneficial effects of EES and gene therapy would need to be confirmed in male rats.

Study Limitations

  • 1
    The implantation of 12-channel headplugs fixed on the animal skull restricted our possibility in using standard BBB test for evaluation of functional recovery.
  • 2
    A small number of animals in this proof of concept study would make the interpretation of results from complex locomotor behavioral testing like BBB even harder.
  • 3
    Due to the ease and consistency of bladder management after SCI, only female rats were used in this study.

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