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

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

International journal of molecular sciences, 2020-11, Vol.21 (23), p.8896 [Periódico revisado por pares]

Switzerland: MDPI AG

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Título:
Epidural Stimulation Combined with Triple Gene Therapy for Spinal Cord Injury Treatment
Autor: Islamov, Rustem ; Bashirov, Farid ; Fadeev, Filip ; Shevchenko, Roman ; Izmailov, Andrei ; Markosyan, Vage ; Sokolov, Mikhail ; Kuznetsov, Maksim ; Davleeva, Maria ; Garifulin, Ravil ; Salafutdinov, Ilnur ; Nurullin, Leniz ; Chelyshev, Yuriy ; Lavrov, Igor
Assuntos: adenoviral vector ; Adenoviridae - genetics ; Animal models ; Animals ; Ankle ; Cell adhesion ; Cell adhesion & migration ; Cell adhesion molecules ; Cell- and Tissue-Based Therapy - methods ; cell-mediated gene therapy ; Clinical trials ; Cord blood ; Disease Models, Animal ; Electric Stimulation Therapy ; Electrical stimuli ; Epidural ; epidural electrical stimulation ; Epidural Space ; Gene therapy ; Genetic Therapy - methods ; Genetic Vectors - therapeutic use ; Glial Cell Line-Derived Neurotrophic Factor - genetics ; Glial Cell Line-Derived Neurotrophic Factor - therapeutic use ; Glial cells ; Growth factors ; Hogs ; human umbilical cord blood mononuclear cell ; Humans ; Leukocytes (mononuclear) ; Motor Activity - genetics ; Motor Activity - physiology ; Motor task performance ; Muscles ; Neural cell adhesion molecule ; Neural Cell Adhesion Molecules - genetics ; Neural Cell Adhesion Molecules - therapeutic use ; Neurogenesis ; Neuroglia - transplantation ; Neuronal-glial interactions ; Neurotrophic factors ; Physiology ; pigs ; Recovery of Function - genetics ; Recovery of Function - radiation effects ; Skeletal muscle ; Spinal cord ; Spinal Cord - physiopathology ; Spinal Cord - radiation effects ; Spinal cord injuries ; Spinal Cord Injuries - genetics ; Spinal Cord Injuries - physiopathology ; Spinal Cord Injuries - therapy ; Spinal cord injury ; Spinal injuries ; Stimulation ; Surgery ; Swine ; Swine - genetics ; Training ; Translation ; Umbilical cord ; Vascular endothelial growth factor ; Vascular Endothelial Growth Factor A - genetics ; Vascular Endothelial Growth Factor A - therapeutic use
É parte de: International journal of molecular sciences, 2020-11, Vol.21 (23), p.8896
Descrição: 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.
Editor: Switzerland: MDPI AG
Idioma: Inglês

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

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

Switzerland: MDPI AG

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