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 encodin...
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| Language: | English |
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MDPI AG
2022-01-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/1/144 |
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| author | Rustem Islamov Farid Bashirov Andrei Izmailov Filip Fadeev Vage Markosyan Mikhail Sokolov Maksim Shmarov Denis Logunov Boris Naroditsky Igor Lavrov |
| author_facet | Rustem Islamov Farid Bashirov Andrei Izmailov Filip Fadeev Vage Markosyan Mikhail Sokolov Maksim Shmarov Denis Logunov Boris Naroditsky Igor Lavrov |
| author_sort | Rustem Islamov |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T03:45:51Z |
| format | Article |
| id | doaj.art-daca89697fcb443ab3932a4e1430df9d |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T03:45:51Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-daca89697fcb443ab3932a4e1430df9d2023-11-23T11:20:51ZengMDPI AGCells2073-44092022-01-0111114410.3390/cells11010144New Therapy for Spinal Cord Injury: Autologous Genetically-Enriched Leucoconcentrate Integrated with Epidural Electrical StimulationRustem Islamov0Farid Bashirov1Andrei Izmailov2Filip Fadeev3Vage Markosyan4Mikhail Sokolov5Maksim Shmarov6Denis Logunov7Boris Naroditsky8Igor Lavrov9Department of Medical biology and Genetics, Kazan State Medical University, 420012 Kazan, RussiaDepartment of Medical biology and Genetics, Kazan State Medical University, 420012 Kazan, RussiaDepartment of Medical biology and Genetics, Kazan State Medical University, 420012 Kazan, RussiaDepartment of Medical biology and Genetics, Kazan State Medical University, 420012 Kazan, RussiaDepartment of Medical biology and Genetics, Kazan State Medical University, 420012 Kazan, RussiaDepartment of Medical biology and Genetics, Kazan State Medical University, 420012 Kazan, RussiaThe 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, RussiaThe 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, RussiaThe 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, RussiaCenter for Neurobiology and Brain Restoration, Skolkovo Institute of Science and Technology, 121205 Moscow, RussiaThe 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.https://www.mdpi.com/2073-4409/11/1/144autologous genetically-enriched leucoconcentratechimeric adenoviral vectorvascular endothelial growth factorglial cell line-derived neurotrophic factorneural cell adhesion moleculespinal cord contusion injury |
| spellingShingle | Rustem Islamov Farid Bashirov Andrei Izmailov Filip Fadeev Vage Markosyan Mikhail Sokolov Maksim Shmarov Denis Logunov Boris Naroditsky Igor Lavrov New Therapy for Spinal Cord Injury: Autologous Genetically-Enriched Leucoconcentrate Integrated with Epidural Electrical Stimulation Cells autologous genetically-enriched leucoconcentrate chimeric adenoviral vector vascular endothelial growth factor glial cell line-derived neurotrophic factor neural cell adhesion molecule spinal cord contusion injury |
| title | New Therapy for Spinal Cord Injury: Autologous Genetically-Enriched Leucoconcentrate Integrated with Epidural Electrical Stimulation |
| title_full | New Therapy for Spinal Cord Injury: Autologous Genetically-Enriched Leucoconcentrate Integrated with Epidural Electrical Stimulation |
| title_fullStr | New Therapy for Spinal Cord Injury: Autologous Genetically-Enriched Leucoconcentrate Integrated with Epidural Electrical Stimulation |
| title_full_unstemmed | New Therapy for Spinal Cord Injury: Autologous Genetically-Enriched Leucoconcentrate Integrated with Epidural Electrical Stimulation |
| title_short | New Therapy for Spinal Cord Injury: Autologous Genetically-Enriched Leucoconcentrate Integrated with Epidural Electrical Stimulation |
| title_sort | new therapy for spinal cord injury autologous genetically enriched leucoconcentrate integrated with epidural electrical stimulation |
| topic | autologous genetically-enriched leucoconcentrate chimeric adenoviral vector vascular endothelial growth factor glial cell line-derived neurotrophic factor neural cell adhesion molecule spinal cord contusion injury |
| url | https://www.mdpi.com/2073-4409/11/1/144 |
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