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Extracellular vesicles of human glial cells exert neuroprotective effects via brain miRNA modulation in a rat model of traumatic brain injury

Stem cell-based therapeutic approaches for neurological disorders are widely studied. Paracrine factors secreted by stem cells in vitro and delivered intranasally might allow bypassing the disadvantages associated with a surgical cell delivery procedure with likely immune rejection of a transplant....

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Autores principales: Salikhova, Diana I., Timofeeva, Angelika V., Golovicheva, Victoria V., Fatkhudinov, Timur Kh., Shevtsova, Yulia A., Soboleva, Anna G., Fedorov, Ivan S., Goryunov, Kirill V., Dyakonov, Alexander S., Mokrousova, Victoria O., Shedenkova, Margarita O., Elchaninov, Andrey V., Makhnach, Oleg V., Kutsev, Sergey I., Chekhonin, Vladimir P., Silachev, Denis N., Goldshtein, Dmitry V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10663567/
https://www.ncbi.nlm.nih.gov/pubmed/37989873
http://dx.doi.org/10.1038/s41598-023-47627-2
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author Salikhova, Diana I.
Timofeeva, Angelika V.
Golovicheva, Victoria V.
Fatkhudinov, Timur Kh.
Shevtsova, Yulia A.
Soboleva, Anna G.
Fedorov, Ivan S.
Goryunov, Kirill V.
Dyakonov, Alexander S.
Mokrousova, Victoria O.
Shedenkova, Margarita O.
Elchaninov, Andrey V.
Makhnach, Oleg V.
Kutsev, Sergey I.
Chekhonin, Vladimir P.
Silachev, Denis N.
Goldshtein, Dmitry V.
author_facet Salikhova, Diana I.
Timofeeva, Angelika V.
Golovicheva, Victoria V.
Fatkhudinov, Timur Kh.
Shevtsova, Yulia A.
Soboleva, Anna G.
Fedorov, Ivan S.
Goryunov, Kirill V.
Dyakonov, Alexander S.
Mokrousova, Victoria O.
Shedenkova, Margarita O.
Elchaninov, Andrey V.
Makhnach, Oleg V.
Kutsev, Sergey I.
Chekhonin, Vladimir P.
Silachev, Denis N.
Goldshtein, Dmitry V.
author_sort Salikhova, Diana I.
collection PubMed
description Stem cell-based therapeutic approaches for neurological disorders are widely studied. Paracrine factors secreted by stem cells in vitro and delivered intranasally might allow bypassing the disadvantages associated with a surgical cell delivery procedure with likely immune rejection of a transplant. In this study, we investigated the therapeutic effect of the extracellular vesicles secreted by glial progenitor cells (GPC-EV) derived from human induced pluripotent stem cell in a traumatic brain injury model. Intranasal administration of GPC-EV to Wistar rats for 6 days improved sensorimotor functions assessed over a 14-day observation period. Beside, deep sequencing of microRNA transcriptome of GPC-EV was estimate, and was revealed 203 microRNA species that might be implicated in prevention of various brain pathologies. Modulation of microRNA pools might contribute to the observed decrease in the number of astrocytes that inhibit neurorecovery processes while enhancing neuroplasticity by decreasing phosphorylated Tau forms, preventing inflammation and apoptosis associated with secondary damage to brain tissue. The course of GPC-EV administration was promoted the increasing protein levels of NF-κB in studied areas of the rat brain, indicating NF-κB dependent mechanisms as a plausible route of neuroprotection within the damaged area. This investigation showed that GPC-EV may be representing a therapeutic approach in traumatic brain injury, though its translation into the clinic would require an additional research and development.
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spelling pubmed-106635672023-11-21 Extracellular vesicles of human glial cells exert neuroprotective effects via brain miRNA modulation in a rat model of traumatic brain injury Salikhova, Diana I. Timofeeva, Angelika V. Golovicheva, Victoria V. Fatkhudinov, Timur Kh. Shevtsova, Yulia A. Soboleva, Anna G. Fedorov, Ivan S. Goryunov, Kirill V. Dyakonov, Alexander S. Mokrousova, Victoria O. Shedenkova, Margarita O. Elchaninov, Andrey V. Makhnach, Oleg V. Kutsev, Sergey I. Chekhonin, Vladimir P. Silachev, Denis N. Goldshtein, Dmitry V. Sci Rep Article Stem cell-based therapeutic approaches for neurological disorders are widely studied. Paracrine factors secreted by stem cells in vitro and delivered intranasally might allow bypassing the disadvantages associated with a surgical cell delivery procedure with likely immune rejection of a transplant. In this study, we investigated the therapeutic effect of the extracellular vesicles secreted by glial progenitor cells (GPC-EV) derived from human induced pluripotent stem cell in a traumatic brain injury model. Intranasal administration of GPC-EV to Wistar rats for 6 days improved sensorimotor functions assessed over a 14-day observation period. Beside, deep sequencing of microRNA transcriptome of GPC-EV was estimate, and was revealed 203 microRNA species that might be implicated in prevention of various brain pathologies. Modulation of microRNA pools might contribute to the observed decrease in the number of astrocytes that inhibit neurorecovery processes while enhancing neuroplasticity by decreasing phosphorylated Tau forms, preventing inflammation and apoptosis associated with secondary damage to brain tissue. The course of GPC-EV administration was promoted the increasing protein levels of NF-κB in studied areas of the rat brain, indicating NF-κB dependent mechanisms as a plausible route of neuroprotection within the damaged area. This investigation showed that GPC-EV may be representing a therapeutic approach in traumatic brain injury, though its translation into the clinic would require an additional research and development. Nature Publishing Group UK 2023-11-21 /pmc/articles/PMC10663567/ /pubmed/37989873 http://dx.doi.org/10.1038/s41598-023-47627-2 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Salikhova, Diana I.
Timofeeva, Angelika V.
Golovicheva, Victoria V.
Fatkhudinov, Timur Kh.
Shevtsova, Yulia A.
Soboleva, Anna G.
Fedorov, Ivan S.
Goryunov, Kirill V.
Dyakonov, Alexander S.
Mokrousova, Victoria O.
Shedenkova, Margarita O.
Elchaninov, Andrey V.
Makhnach, Oleg V.
Kutsev, Sergey I.
Chekhonin, Vladimir P.
Silachev, Denis N.
Goldshtein, Dmitry V.
Extracellular vesicles of human glial cells exert neuroprotective effects via brain miRNA modulation in a rat model of traumatic brain injury
title Extracellular vesicles of human glial cells exert neuroprotective effects via brain miRNA modulation in a rat model of traumatic brain injury
title_full Extracellular vesicles of human glial cells exert neuroprotective effects via brain miRNA modulation in a rat model of traumatic brain injury
title_fullStr Extracellular vesicles of human glial cells exert neuroprotective effects via brain miRNA modulation in a rat model of traumatic brain injury
title_full_unstemmed Extracellular vesicles of human glial cells exert neuroprotective effects via brain miRNA modulation in a rat model of traumatic brain injury
title_short Extracellular vesicles of human glial cells exert neuroprotective effects via brain miRNA modulation in a rat model of traumatic brain injury
title_sort extracellular vesicles of human glial cells exert neuroprotective effects via brain mirna modulation in a rat model of traumatic brain injury
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10663567/
https://www.ncbi.nlm.nih.gov/pubmed/37989873
http://dx.doi.org/10.1038/s41598-023-47627-2
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