International Journal of Molecular Sciences (Nov 2020)

Epidural Stimulation Combined with Triple Gene Therapy for Spinal Cord Injury Treatment

  • Rustem Islamov,
  • Farid Bashirov,
  • Filip Fadeev,
  • Roman Shevchenko,
  • Andrei Izmailov,
  • Vage Markosyan,
  • Mikhail Sokolov,
  • Maksim Kuznetsov,
  • Maria Davleeva,
  • Ravil Garifulin,
  • Ilnur Salafutdinov,
  • Leniz Nurullin,
  • Yuriy Chelyshev,
  • Igor Lavrov

DOI
https://doi.org/10.3390/ijms21238896
Journal volume & issue
Vol. 21, no. 23
p. 8896

Abstract

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The translation of new therapies for spinal cord injury to clinical trials can be facilitated with large animal models close in morpho-physiological scale to humans. Here, we report functional restoration and morphological reorganization after spinal contusion in pigs, following a combined treatment of locomotor training facilitated with epidural electrical stimulation (EES) and cell-mediated triple gene therapy with umbilical cord blood mononuclear cells overexpressing recombinant vascular endothelial growth factor, glial-derived neurotrophic factor, and neural cell adhesion molecule. Preliminary results obtained on a small sample of pigs 2 months after spinal contusion revealed the difference in post-traumatic spinal cord outcomes in control and treated animals. In treated pigs, motor performance was enabled by EES and the corresponding morpho-functional changes in hind limb skeletal muscles were accompanied by the reorganization of the glial cell, the reaction of stress cell, and synaptic proteins. Our data demonstrate effects of combined EES-facilitated motor training and cell-mediated triple gene therapy after spinal contusion in large animals, informing a background for further animal studies and clinical translation.

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