New Therapy for Spinal Cord Injury: Autologous Genetically-Enriched Leucoconcentrate Integrated with Epidural Electrical Stimulation
Rustem Islamov,
Farid Bashirov,
Andrei Izmailov,
Filip Fadeev,
Vage Markosyan,
Mikhail Sokolov,
Maksim Shmarov,
Denis Logunov,
Boris Naroditsky,
Igor Lavrov
Affiliations
Rustem Islamov
Department of Medical biology and Genetics, Kazan State Medical University, 420012 Kazan, Russia
Farid Bashirov
Department of Medical biology and Genetics, Kazan State Medical University, 420012 Kazan, Russia
Andrei Izmailov
Department of Medical biology and Genetics, Kazan State Medical University, 420012 Kazan, Russia
Filip Fadeev
Department of Medical biology and Genetics, Kazan State Medical University, 420012 Kazan, Russia
Vage Markosyan
Department of Medical biology and Genetics, Kazan State Medical University, 420012 Kazan, Russia
Mikhail Sokolov
Department of Medical biology and Genetics, Kazan State Medical University, 420012 Kazan, Russia
Maksim Shmarov
The National Research Center for Epidemiology and Microbiology Named after Honorary Academician N.F. Gamaleya of the Ministry of Health of the Russian Federation, 123098 Moscow, Russia
Denis Logunov
The National Research Center for Epidemiology and Microbiology Named after Honorary Academician N.F. Gamaleya of the Ministry of Health of the Russian Federation, 123098 Moscow, Russia
Boris Naroditsky
The National Research Center for Epidemiology and Microbiology Named after Honorary Academician N.F. Gamaleya of the Ministry of Health of the Russian Federation, 123098 Moscow, Russia
Igor Lavrov
Center for Neurobiology and Brain Restoration, Skolkovo Institute of Science and Technology, 121205 Moscow, Russia
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.
