New Therapy for Spinal Cord Injury: Autologous Genetically-Enriched Leucoconcentrate Integrated with Epidural Electrical Stimulation

The contemporary strategy for spinal cord injury (SCI) therapy aims to combine multiple approaches to control pathogenic mechanisms of neurodegeneration and stimulate neuroregeneration. In this study, a novel regenerative approach using an autologous leucoconcentrate enriched with transgenes encoding vascular endothelial growth factor (VEGF), glial cell line-derived neurotrophic factor (GDNF), and neural cell adhesion molecule (NCAM) combined with supra- and sub-lesional epidural electrical stimulation (EES) was tested on mini-pigs similar in morpho-physiological scale to humans. The complex analysis of the spinal cord recovery after a moderate contusion injury in treated mini-pigs compared to control animals revealed: better performance in behavioural and joint kinematics, restoration of electromyography characteristics, and improvement in selected immunohistology features related to cell survivability, synaptic protein expression, and glial reorganization above and below the injury. These results for the first time demonstrate the positive effect of intravenous infusion of autologous genetically-enriched leucoconcentrate producing recombinant molecules stimulating neuroregeneration combined with neuromodulation by translesional multisite EES on the restoration of the post-traumatic spinal cord in mini-pigs and suggest the high translational potential of this novel regenerative therapy for SCI patients.

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Faculty Opinions recommendation of Effect of vascular endothelial growth factor treatment in experimental traumatic spinal cord injury: in vivo longitudinal assessment.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.9908956.11172056 ◽

2011 ◽

Author(s):

Jose V Lafuente ◽

Enrike Argandoña

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Vascular Endothelial Growth Factor ◽

Traumatic Spinal Cord Injury ◽

Vascular Endothelial ◽

Longitudinal Assessment ◽

Cord Injury ◽

Endothelial Growth Factor ◽

Growth Factor Treatment

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Combined Supra- and Sub-Lesional Epidural Electrical Stimulation for Restoration of the Motor Functions after Spinal Cord Injury in Mini Pigs

Brain Sciences ◽

10.3390/brainsci10100744 ◽

2020 ◽

Vol 10 (10) ◽

pp. 744

Author(s):

Filip Fadeev ◽

Anton Eremeev ◽

Farid Bashirov ◽

Roman Shevchenko ◽

Andrei Izmailov ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Electrical Stimulation ◽

Motor Evoked Potentials ◽

Functional Restoration ◽

Thoracic Injury ◽

Spinal Circuitry ◽

Lower Amplitude ◽

Cord Injury ◽

Mini Pigs

This study evaluates the effect of combined epidural electrical stimulation (EES) applied above (C5) and below (L2) the spinal cord injury (SCI) at T8–9 combined with motor training on the restoration of sensorimotor function in mini pigs. The motor evoked potentials (MEP) induced by EES applied at C5 and L2 levels were recorded in soleus muscles before and two weeks after SCI. EES treatment started two weeks after SCI and continued for 6 weeks led to improvement in multiple metrics, including behavioral, electrophysiological, and joint kinematics outcomes. In control animals after SCI a multiphasic M-response was observed during M/H-response testing, while animals received EES-enable training demonstrated the restoration of the M-response and H-reflex, although at a lower amplitude. The joint kinematic and assessment with Porcine Thoracic Injury Behavior scale (PTIBS) motor recovery scale demonstrated improvement in animals that received EES-enable training compared to animals with no treatment. The positive effect of two-level (cervical and lumbar) epidural electrical stimulation on functional restoration in mini pigs following spinal cord contusion injury in mini pigs could be related with facilitation of spinal circuitry at both levels and activation of multisegmental coordination. This approach can be taken as a basis for the future development of neuromodulation and neurorehabilitation therapy for patients with spinal cord injury.

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