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Enhancing Functional Recovery Through Intralesional Application of Extracellular Vesicles in a Rat Model of Traumatic Spinal Cord Injury

Local inflammation plays a pivotal role in the process of secondary damage after spinal cord injury. We recently reported that acute intravenous application of extracellular vesicles (EVs) secreted by human umbilical cord mesenchymal stromal cells dampens the induction of inflammatory processes foll...

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Autores principales: Romanelli, Pasquale, Bieler, Lara, Heimel, Patrick, Škokić, Siniša, Jakubecova, Dominika, Kreutzer, Christina, Zaunmair, Pia, Smolčić, Tomislav, Benedetti, Bruno, Rohde, Eva, Gimona, Mario, Hercher, David, Dobrivojević Radmilović, Marina, Couillard-Despres, Sebastien
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8762366/
https://www.ncbi.nlm.nih.gov/pubmed/35046776
http://dx.doi.org/10.3389/fncel.2021.795008
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author Romanelli, Pasquale
Bieler, Lara
Heimel, Patrick
Škokić, Siniša
Jakubecova, Dominika
Kreutzer, Christina
Zaunmair, Pia
Smolčić, Tomislav
Benedetti, Bruno
Rohde, Eva
Gimona, Mario
Hercher, David
Dobrivojević Radmilović, Marina
Couillard-Despres, Sebastien
author_facet Romanelli, Pasquale
Bieler, Lara
Heimel, Patrick
Škokić, Siniša
Jakubecova, Dominika
Kreutzer, Christina
Zaunmair, Pia
Smolčić, Tomislav
Benedetti, Bruno
Rohde, Eva
Gimona, Mario
Hercher, David
Dobrivojević Radmilović, Marina
Couillard-Despres, Sebastien
author_sort Romanelli, Pasquale
collection PubMed
description Local inflammation plays a pivotal role in the process of secondary damage after spinal cord injury. We recently reported that acute intravenous application of extracellular vesicles (EVs) secreted by human umbilical cord mesenchymal stromal cells dampens the induction of inflammatory processes following traumatic spinal cord injury. However, systemic application of EVs is associated with delayed delivery to the site of injury and the necessity for high doses to reach therapeutic levels locally. To resolve these two constraints, we injected EVs directly at the lesion site acutely after spinal cord injury. We report here that intralesional application of EVs resulted in a more robust improvement of motor recovery, assessed with the BBB score and sub-score, as compared to the intravenous delivery. Moreover, the intralesional application was more potent in reducing inflammation and scarring after spinal cord injury than intravenous administration. Hence, the development of EV-based therapy for spinal cord injury should aim at an early application of vesicles close to the lesion.
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spelling pubmed-87623662022-01-18 Enhancing Functional Recovery Through Intralesional Application of Extracellular Vesicles in a Rat Model of Traumatic Spinal Cord Injury Romanelli, Pasquale Bieler, Lara Heimel, Patrick Škokić, Siniša Jakubecova, Dominika Kreutzer, Christina Zaunmair, Pia Smolčić, Tomislav Benedetti, Bruno Rohde, Eva Gimona, Mario Hercher, David Dobrivojević Radmilović, Marina Couillard-Despres, Sebastien Front Cell Neurosci Cellular Neuroscience Local inflammation plays a pivotal role in the process of secondary damage after spinal cord injury. We recently reported that acute intravenous application of extracellular vesicles (EVs) secreted by human umbilical cord mesenchymal stromal cells dampens the induction of inflammatory processes following traumatic spinal cord injury. However, systemic application of EVs is associated with delayed delivery to the site of injury and the necessity for high doses to reach therapeutic levels locally. To resolve these two constraints, we injected EVs directly at the lesion site acutely after spinal cord injury. We report here that intralesional application of EVs resulted in a more robust improvement of motor recovery, assessed with the BBB score and sub-score, as compared to the intravenous delivery. Moreover, the intralesional application was more potent in reducing inflammation and scarring after spinal cord injury than intravenous administration. Hence, the development of EV-based therapy for spinal cord injury should aim at an early application of vesicles close to the lesion. Frontiers Media S.A. 2022-01-03 /pmc/articles/PMC8762366/ /pubmed/35046776 http://dx.doi.org/10.3389/fncel.2021.795008 Text en Copyright © 2022 Romanelli, Bieler, Heimel, Škokić, Jakubecova, Kreutzer, Zaunmair, Smolčić, Benedetti, Rohde, Gimona, Hercher, Dobrivojević Radmilović and Couillard-Despres. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cellular Neuroscience
Romanelli, Pasquale
Bieler, Lara
Heimel, Patrick
Škokić, Siniša
Jakubecova, Dominika
Kreutzer, Christina
Zaunmair, Pia
Smolčić, Tomislav
Benedetti, Bruno
Rohde, Eva
Gimona, Mario
Hercher, David
Dobrivojević Radmilović, Marina
Couillard-Despres, Sebastien
Enhancing Functional Recovery Through Intralesional Application of Extracellular Vesicles in a Rat Model of Traumatic Spinal Cord Injury
title Enhancing Functional Recovery Through Intralesional Application of Extracellular Vesicles in a Rat Model of Traumatic Spinal Cord Injury
title_full Enhancing Functional Recovery Through Intralesional Application of Extracellular Vesicles in a Rat Model of Traumatic Spinal Cord Injury
title_fullStr Enhancing Functional Recovery Through Intralesional Application of Extracellular Vesicles in a Rat Model of Traumatic Spinal Cord Injury
title_full_unstemmed Enhancing Functional Recovery Through Intralesional Application of Extracellular Vesicles in a Rat Model of Traumatic Spinal Cord Injury
title_short Enhancing Functional Recovery Through Intralesional Application of Extracellular Vesicles in a Rat Model of Traumatic Spinal Cord Injury
title_sort enhancing functional recovery through intralesional application of extracellular vesicles in a rat model of traumatic spinal cord injury
topic Cellular Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8762366/
https://www.ncbi.nlm.nih.gov/pubmed/35046776
http://dx.doi.org/10.3389/fncel.2021.795008
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