Mesenchymal stem cells secretome-induced axonal outgrowth is mediated by BDNF

Detalhes bibliográficos
Autor(a) principal: Martins, Luís F.
Data de Publicação: 2017
Outros Autores: Costa, Rui O., Pedro, Joana R., Aguiar, Paulo, Serra, Sofia Cravino, Teixeira, Fábio Gabriel Rodrigues, Sousa, Nuno, Salgado, A. J., Almeida, Ramiro D.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/1822/49647
Resumo: Mesenchymal stem cells (MSCs) have been used for cell-based therapies in regenerative medicine, with increasing importance in central and peripheral nervous system repair. However, MSCs grafting present disadvantages, such as, a high number of cells required for transplantation and low survival rate when transplanted into the central nervous system (CNS). In line with this, MSCs secretome which present on its composition a wide range of molecules (neurotrophins, cytokines) and microvesicles, can be a solution to surpass these problems. However, the effect of MSCs secretome in axonal elongation is poorly understood. In this study, we demonstrate that application of MSCs secretome to both rat cortical and hippocampal neurons induces an increase in axonal length. In addition, we show that this growth effect is axonal intrinsic with no contribution from the cell body. To further understand which are the molecules required for secretome-induced axonal outgrowth effect, we depleted brain-derived neurotrophic factor (BDNF) from the secretome. Our results show that in the absence of BDNF, secretome-induced axonal elongation effect is lost and that axons present a reduced axonal growth rate. Altogether, our results demonstrate that MSCs secretome is able to promote axonal outgrowth in CNS neurons and this effect is mediated by BDNF.
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spelling Mesenchymal stem cells secretome-induced axonal outgrowth is mediated by BDNFCiências Médicas::Medicina BásicaScience & TechnologyMesenchymal stem cells (MSCs) have been used for cell-based therapies in regenerative medicine, with increasing importance in central and peripheral nervous system repair. However, MSCs grafting present disadvantages, such as, a high number of cells required for transplantation and low survival rate when transplanted into the central nervous system (CNS). In line with this, MSCs secretome which present on its composition a wide range of molecules (neurotrophins, cytokines) and microvesicles, can be a solution to surpass these problems. However, the effect of MSCs secretome in axonal elongation is poorly understood. In this study, we demonstrate that application of MSCs secretome to both rat cortical and hippocampal neurons induces an increase in axonal length. In addition, we show that this growth effect is axonal intrinsic with no contribution from the cell body. To further understand which are the molecules required for secretome-induced axonal outgrowth effect, we depleted brain-derived neurotrophic factor (BDNF) from the secretome. Our results show that in the absence of BDNF, secretome-induced axonal elongation effect is lost and that axons present a reduced axonal growth rate. Altogether, our results demonstrate that MSCs secretome is able to promote axonal outgrowth in CNS neurons and this effect is mediated by BDNF.European Regional Development Fund (ERDF), through the Centro 2020 Regional Operational Programme under project CENTRO-01–0145-FEDER-000008:BrainHealth 2020, and through the COMPETE 2020 - Operational Programme for Competitiveness and Internationalisation and Portuguese national funds via FCT – Fundação para a Ciência e a Tecnologia, I.P., under projects PTDC/SAU-NEU/104100/2008, EXPL/NEU-NMC/0541/2012 and UID/NEU/04539/2013. This work was also funded by Marie Curie Actions - International reintegration grant #249288, 7th Framework programme, EU. Partially funded by Prémios Santa Casa Neurociências - Prize Melo e Castro for Spinal Cord Injury Research; Portuguese Foundation for Science and Technology (IF Development Grant to A.J.S.); NORTE-01-0145-FEDER-000013, supported by the Northern Portugal Regional Operational Programme; by FEDER funds, through the Competitiveness Factors Operational Programme (COMPETE), and by national funds, through the Foundation for Science and Technology (FCT), under the scope of the project POCI-01-0145-FEDER-007038. The authors would also like to acknowledge Prof. J.E. Davies from the Institute of Biomaterials and Biomedical Engineering at the University of Toronto, Canada, for kindly providing some of the HUCPVCs lots used in the present workinfo:eu-repo/semantics/publishedVersionNature Publishing GroupUniversidade do MinhoMartins, Luís F.Costa, Rui O.Pedro, Joana R.Aguiar, PauloSerra, Sofia CravinoTeixeira, Fábio Gabriel RodriguesSousa, NunoSalgado, A. J.Almeida, Ramiro D.2017-06-232017-06-23T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/49647engMartins, L. F., Costa, R. O., Pedro, J. R., Aguiar, P., Serra, S. C., Teixeira, F. G., ... & Almeida, R. D. (2017). Mesenchymal stem cells secretome-induced axonal outgrowth is mediated by BDNF. Scientific Reports, 7(1), 4153.1662-51532045-232210.1038/s41598-017-03592-128646200https://www.nature.com/articles/s41598-017-03592-1info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-21T12:28:26Zoai:repositorium.sdum.uminho.pt:1822/49647Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:23:15.092970Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Mesenchymal stem cells secretome-induced axonal outgrowth is mediated by BDNF
title Mesenchymal stem cells secretome-induced axonal outgrowth is mediated by BDNF
spellingShingle Mesenchymal stem cells secretome-induced axonal outgrowth is mediated by BDNF
Martins, Luís F.
Ciências Médicas::Medicina Básica
Science & Technology
title_short Mesenchymal stem cells secretome-induced axonal outgrowth is mediated by BDNF
title_full Mesenchymal stem cells secretome-induced axonal outgrowth is mediated by BDNF
title_fullStr Mesenchymal stem cells secretome-induced axonal outgrowth is mediated by BDNF
title_full_unstemmed Mesenchymal stem cells secretome-induced axonal outgrowth is mediated by BDNF
title_sort Mesenchymal stem cells secretome-induced axonal outgrowth is mediated by BDNF
author Martins, Luís F.
author_facet Martins, Luís F.
Costa, Rui O.
Pedro, Joana R.
Aguiar, Paulo
Serra, Sofia Cravino
Teixeira, Fábio Gabriel Rodrigues
Sousa, Nuno
Salgado, A. J.
Almeida, Ramiro D.
author_role author
author2 Costa, Rui O.
Pedro, Joana R.
Aguiar, Paulo
Serra, Sofia Cravino
Teixeira, Fábio Gabriel Rodrigues
Sousa, Nuno
Salgado, A. J.
Almeida, Ramiro D.
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade do Minho
dc.contributor.author.fl_str_mv Martins, Luís F.
Costa, Rui O.
Pedro, Joana R.
Aguiar, Paulo
Serra, Sofia Cravino
Teixeira, Fábio Gabriel Rodrigues
Sousa, Nuno
Salgado, A. J.
Almeida, Ramiro D.
dc.subject.por.fl_str_mv Ciências Médicas::Medicina Básica
Science & Technology
topic Ciências Médicas::Medicina Básica
Science & Technology
description Mesenchymal stem cells (MSCs) have been used for cell-based therapies in regenerative medicine, with increasing importance in central and peripheral nervous system repair. However, MSCs grafting present disadvantages, such as, a high number of cells required for transplantation and low survival rate when transplanted into the central nervous system (CNS). In line with this, MSCs secretome which present on its composition a wide range of molecules (neurotrophins, cytokines) and microvesicles, can be a solution to surpass these problems. However, the effect of MSCs secretome in axonal elongation is poorly understood. In this study, we demonstrate that application of MSCs secretome to both rat cortical and hippocampal neurons induces an increase in axonal length. In addition, we show that this growth effect is axonal intrinsic with no contribution from the cell body. To further understand which are the molecules required for secretome-induced axonal outgrowth effect, we depleted brain-derived neurotrophic factor (BDNF) from the secretome. Our results show that in the absence of BDNF, secretome-induced axonal elongation effect is lost and that axons present a reduced axonal growth rate. Altogether, our results demonstrate that MSCs secretome is able to promote axonal outgrowth in CNS neurons and this effect is mediated by BDNF.
publishDate 2017
dc.date.none.fl_str_mv 2017-06-23
2017-06-23T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/1822/49647
url http://hdl.handle.net/1822/49647
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Martins, L. F., Costa, R. O., Pedro, J. R., Aguiar, P., Serra, S. C., Teixeira, F. G., ... & Almeida, R. D. (2017). Mesenchymal stem cells secretome-induced axonal outgrowth is mediated by BDNF. Scientific Reports, 7(1), 4153.
1662-5153
2045-2322
10.1038/s41598-017-03592-1
28646200
https://www.nature.com/articles/s41598-017-03592-1
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
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