Application of adipose-derived mesenchymal stem cells in an in vivo model of peripheral nerve damage

[EN] Background: Neuropathic pain is one of the most difficult to treat chronic pain syndromes. It has significant effects on patients’ quality of life and substantially adds to the burden of direct and indirect medical costs. There is a critical need to improve therapies for peripheral nerve regene...

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Autores: González Cubero, Elsa, González Fernández, María Luisa, Rodríguez Díaz, María, Palomo Irigoyen, Marta, Woodhoo, Ashwin, Villar Suárez, María Vega
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Ajuntament de Barcelona
Repositorio:BULERIA. Repositorio Institucional de la Universidad de León
OAI Identifier:oai:buleria.unileon.es:10612/18488
Acceso en línea:https://www.frontiersin.org/articles/10.3389/fncel.2022.992221/full
https://hdl.handle.net/10612/18488
Access Level:acceso abierto
Palabra clave:Biotecnología
Medicina. Salud
Adipose tissue derived-mesenchymal stem cells
Schwann cells
Peripheral neuropathy
Conditioned medium
Peripheral nerve regeneration
Nerve regeneration using mesenchymal stem cells
2407 Biología Celular
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oai_identifier_str oai:buleria.unileon.es:10612/18488
network_acronym_str ES
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repository_id_str
spelling Application of adipose-derived mesenchymal stem cells in an in vivo model of peripheral nerve damageGonzález Cubero, ElsaGonzález Fernández, María LuisaRodríguez Díaz, MaríaPalomo Irigoyen, MartaWoodhoo, AshwinVillar Suárez, María VegaBiotecnologíaMedicina. SaludAdipose tissue derived-mesenchymal stem cellsSchwann cellsPeripheral neuropathyConditioned mediumPeripheral nerve regenerationNerve regeneration using mesenchymal stem cells2407 Biología Celular[EN] Background: Neuropathic pain is one of the most difficult to treat chronic pain syndromes. It has significant effects on patients’ quality of life and substantially adds to the burden of direct and indirect medical costs. There is a critical need to improve therapies for peripheral nerve regeneration. The aim of this study is to address this issue by performing a detailed analysis of the therapeutic benefits of two treatment options: adipose tissue derived-mesenchymal stem cells (ASCs) and ASC-conditioned medium (CM). Methods: To this end, we used an in vivo rat sciatic nerve damage model to investigate the molecular mechanisms involved in the myelinating capacity of ASCs and CM. Furthermore, effect of TNF and CM on Schwann cells (SCs) was evaluated. For our in vivo model, biomaterial surgical implants containing TNF were used to induce peripheral neuropathy in rats. Damaged nerves were also treated with either ASCs or CM and molecular methods were used to collect evidence of nerve regeneration. Post-operatively, rats were subjected to walking track analysis and their sciatic functional index was evaluated. Morphological data was gathered through transmission electron microscopy (TEM) of sciatic nerves harvested from the experimental rats. We also evaluated the effect of TNF on Schwann cells (SCs) in vitro. Genes and their correspondent proteins associated with nerve regeneration were analyzed by qPCR, western blot, and confocal microscopy. Results: Our data suggests that both ASCs and CM are potentially beneficial treatments for promoting myelination and axonal regeneration. After TNF-induced nerve damage we observed an upregulation of c-Jun along with a downregulation of Krox-20 myelin-associated transcription factor. However, when CM was added to TNF-treated nerves the opposite effect occurred and also resulted in increased expression of myelin-related genes and their corresponding proteins. Conclusion: Findings from our in vivo model showed that both ASCs and CM aided the regeneration of axonal myelin sheaths and the remodeling of peripheral nerve morphologySIThis study was supported by the Fundación Leonesa ProNeurociencias. The AW’s Lab was supported by AEI/FEDER, EU (RTI2018-097503-B-I00) and the European Community’s H2020 Framework Program ERC Consolidator Grant (865157- MYERIBO)FrontiersMedicina y Cirugia AnimalFacultad de Veterinaria2022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://www.frontiersin.org/articles/10.3389/fncel.2022.992221/fullhttps://hdl.handle.net/10612/18488reponame:BULERIA. Repositorio Institucional de la Universidad de Leóninstname:Ajuntament de BarcelonaInglésinfo:eu-repo/grantAgreement/AEI/Programa Estatal de I+D+i Orientada a los Retos de la Sociedad/RTI2018-097503-B-I00http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:buleria.unileon.es:10612/184882026-06-24T12:43:27Z
dc.title.none.fl_str_mv Application of adipose-derived mesenchymal stem cells in an in vivo model of peripheral nerve damage
title Application of adipose-derived mesenchymal stem cells in an in vivo model of peripheral nerve damage
spellingShingle Application of adipose-derived mesenchymal stem cells in an in vivo model of peripheral nerve damage
González Cubero, Elsa
Biotecnología
Medicina. Salud
Adipose tissue derived-mesenchymal stem cells
Schwann cells
Peripheral neuropathy
Conditioned medium
Peripheral nerve regeneration
Nerve regeneration using mesenchymal stem cells
2407 Biología Celular
title_short Application of adipose-derived mesenchymal stem cells in an in vivo model of peripheral nerve damage
title_full Application of adipose-derived mesenchymal stem cells in an in vivo model of peripheral nerve damage
title_fullStr Application of adipose-derived mesenchymal stem cells in an in vivo model of peripheral nerve damage
title_full_unstemmed Application of adipose-derived mesenchymal stem cells in an in vivo model of peripheral nerve damage
title_sort Application of adipose-derived mesenchymal stem cells in an in vivo model of peripheral nerve damage
dc.creator.none.fl_str_mv González Cubero, Elsa
González Fernández, María Luisa
Rodríguez Díaz, María
Palomo Irigoyen, Marta
Woodhoo, Ashwin
Villar Suárez, María Vega
author González Cubero, Elsa
author_facet González Cubero, Elsa
González Fernández, María Luisa
Rodríguez Díaz, María
Palomo Irigoyen, Marta
Woodhoo, Ashwin
Villar Suárez, María Vega
author_role author
author2 González Fernández, María Luisa
Rodríguez Díaz, María
Palomo Irigoyen, Marta
Woodhoo, Ashwin
Villar Suárez, María Vega
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Medicina y Cirugia Animal
Facultad de Veterinaria
dc.subject.none.fl_str_mv Biotecnología
Medicina. Salud
Adipose tissue derived-mesenchymal stem cells
Schwann cells
Peripheral neuropathy
Conditioned medium
Peripheral nerve regeneration
Nerve regeneration using mesenchymal stem cells
2407 Biología Celular
topic Biotecnología
Medicina. Salud
Adipose tissue derived-mesenchymal stem cells
Schwann cells
Peripheral neuropathy
Conditioned medium
Peripheral nerve regeneration
Nerve regeneration using mesenchymal stem cells
2407 Biología Celular
description [EN] Background: Neuropathic pain is one of the most difficult to treat chronic pain syndromes. It has significant effects on patients’ quality of life and substantially adds to the burden of direct and indirect medical costs. There is a critical need to improve therapies for peripheral nerve regeneration. The aim of this study is to address this issue by performing a detailed analysis of the therapeutic benefits of two treatment options: adipose tissue derived-mesenchymal stem cells (ASCs) and ASC-conditioned medium (CM). Methods: To this end, we used an in vivo rat sciatic nerve damage model to investigate the molecular mechanisms involved in the myelinating capacity of ASCs and CM. Furthermore, effect of TNF and CM on Schwann cells (SCs) was evaluated. For our in vivo model, biomaterial surgical implants containing TNF were used to induce peripheral neuropathy in rats. Damaged nerves were also treated with either ASCs or CM and molecular methods were used to collect evidence of nerve regeneration. Post-operatively, rats were subjected to walking track analysis and their sciatic functional index was evaluated. Morphological data was gathered through transmission electron microscopy (TEM) of sciatic nerves harvested from the experimental rats. We also evaluated the effect of TNF on Schwann cells (SCs) in vitro. Genes and their correspondent proteins associated with nerve regeneration were analyzed by qPCR, western blot, and confocal microscopy. Results: Our data suggests that both ASCs and CM are potentially beneficial treatments for promoting myelination and axonal regeneration. After TNF-induced nerve damage we observed an upregulation of c-Jun along with a downregulation of Krox-20 myelin-associated transcription factor. However, when CM was added to TNF-treated nerves the opposite effect occurred and also resulted in increased expression of myelin-related genes and their corresponding proteins. Conclusion: Findings from our in vivo model showed that both ASCs and CM aided the regeneration of axonal myelin sheaths and the remodeling of peripheral nerve morphology
publishDate 2022
dc.date.none.fl_str_mv 2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://www.frontiersin.org/articles/10.3389/fncel.2022.992221/full
https://hdl.handle.net/10612/18488
url https://www.frontiersin.org/articles/10.3389/fncel.2022.992221/full
https://hdl.handle.net/10612/18488
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv info:eu-repo/grantAgreement/AEI/Programa Estatal de I+D+i Orientada a los Retos de la Sociedad/RTI2018-097503-B-I00
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Frontiers
publisher.none.fl_str_mv Frontiers
dc.source.none.fl_str_mv reponame:BULERIA. Repositorio Institucional de la Universidad de León
instname:Ajuntament de Barcelona
instname_str Ajuntament de Barcelona
reponame_str BULERIA. Repositorio Institucional de la Universidad de León
collection BULERIA. Repositorio Institucional de la Universidad de León
repository.name.fl_str_mv
repository.mail.fl_str_mv
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