Impact of the Secretome of Human Mesenchymal Stem Cells on Brain Structure and Animal behavior in a Rat Model of Parkinson’s Disease
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/1822/49951 |
Resumo: | Research in the last decade strongly suggests that mesenchymal stem cell (MSC)-mediated therapeutic benefits are mainly due to their secretome, which has been proposed as a possible therapeutic tool for the treatment of Parkinson's disease (PD). Indeed, it has been shown that the MSC secretome increases neurogenesis and cell survival, and has numerous neuroprotective actions under different conditions. Additionally, using dynamic culturing conditions (through computer-controlled bioreactors) can further modulate the MSC secretome, thereby generating a more potent neurotrophic factor cocktail (i.e., conditioned medium). In this study, we have characterized the MSC secretome by proteomic-based analysis, investigating its therapeutic effects on the physiological recovery of a 6-hydroxidopamine (6-OHDA) PD rat model. For this purpose, we injected MSC secretome into the substantia nigra (SNc) and striatum (STR), characterizing the behavioral performance and determining histological parameters for injected animals versus untreated groups. We observed that the secretome potentiated the increase of dopaminergic neurons (i.e., tyrosine hydroxylase-positive cells) and neuronal terminals in the SNc and STR, respectively, thereby supporting the recovery observed in the Parkinsonian rats' motor performance outcomes (assessed by rotarod and staircase tests). Finally, proteomic characterization of the MSC secretome (through combined mass spectrometry analysis and Bioplex assays) revealed the presence of important neuroregulatory molecules, namely cystatin C, glia-derived nexin, galectin-1, pigment epithelium-derived factor, vascular endothelial growth factor, brain-derived neurotrophic factor, interleukin-6, and glial cell line-derived neurotrophic factor. Overall, we concluded that the use of human MSC secretome alone was able to partially revert the motor phenotype and the neuronal structure of 6-OHDA PD animals. This indicates that the human MSC secretome could represent a novel therapeutic for the treatment of PD. |
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Impact of the Secretome of Human Mesenchymal Stem Cells on Brain Structure and Animal behavior in a Rat Model of Parkinson’s DiseaseMesenchymal stem cellsParkinson ’ s diseaseSecretomeDopaminergic neuronsNeuroprotectionCiências Médicas::Medicina BásicaScience & TechnologyResearch in the last decade strongly suggests that mesenchymal stem cell (MSC)-mediated therapeutic benefits are mainly due to their secretome, which has been proposed as a possible therapeutic tool for the treatment of Parkinson's disease (PD). Indeed, it has been shown that the MSC secretome increases neurogenesis and cell survival, and has numerous neuroprotective actions under different conditions. Additionally, using dynamic culturing conditions (through computer-controlled bioreactors) can further modulate the MSC secretome, thereby generating a more potent neurotrophic factor cocktail (i.e., conditioned medium). In this study, we have characterized the MSC secretome by proteomic-based analysis, investigating its therapeutic effects on the physiological recovery of a 6-hydroxidopamine (6-OHDA) PD rat model. For this purpose, we injected MSC secretome into the substantia nigra (SNc) and striatum (STR), characterizing the behavioral performance and determining histological parameters for injected animals versus untreated groups. We observed that the secretome potentiated the increase of dopaminergic neurons (i.e., tyrosine hydroxylase-positive cells) and neuronal terminals in the SNc and STR, respectively, thereby supporting the recovery observed in the Parkinsonian rats' motor performance outcomes (assessed by rotarod and staircase tests). Finally, proteomic characterization of the MSC secretome (through combined mass spectrometry analysis and Bioplex assays) revealed the presence of important neuroregulatory molecules, namely cystatin C, glia-derived nexin, galectin-1, pigment epithelium-derived factor, vascular endothelial growth factor, brain-derived neurotrophic factor, interleukin-6, and glial cell line-derived neurotrophic factor. Overall, we concluded that the use of human MSC secretome alone was able to partially revert the motor phenotype and the neuronal structure of 6-OHDA PD animals. This indicates that the human MSC secretome could represent a novel therapeutic for the treatment of PD.Portuguese Foundation for Science and Technology via a Ciência 2007 program and an FCT (Portuguese Foundation for Science and Technology) Investigator development grant (A.J.S.), predoctoral fellowships to F.G.T. (SFRH/69637/2010), and a fellowship to S.A. (SFRH/BD/81495/2011); a Canada Research Chair in Biomedical Engineering (L.A.B.) and a Schulich School of Engineering postdoctoral fellowship (K.M.P.), cofunded by Programa Operacional Regional do Norte (ON.2 – O Novo Norte), under Quadro de Referência Estratégico Nacional (QREN), through Fundo Europeu de Desenvolvimento Regional (FEDER), PEst-C/SAU/LA0001/2013-2014, cofunded by the Programa Operacional Factores de Competitividade, QREN, the European Union (FEDER), and by The National Mass Spectrometry Network under the contract REDE/1506/REM/2005info:eu-repo/semantics/publishedVersionWileyUniversidade do MinhoTeixeira, Fábio Gabriel RodriguesCarvalho, Miguel M.Panchalingam, K. M.Rodrigues, Ana JoãoPinheiro, Bárbara Filipa MendesAnjo, SandraManadas, BrunoBehie, Leo A.Sousa, NunoSalgado, A. J.20172017-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/49951engTeixeira, F. G., Carvalho, M. M., Panchalingam, K. M., Rodrigues, A. J., Mendes‐Pinheiro, B., Anjo, S., ... & Salgado, A. J. (2017). Impact of the secretome of human mesenchymal stem cells on brain structure and animal behavior in a rat model of Parkinson's disease. Stem cells translational medicine, 6(2), 634-6462157-65642157-658010.5966/sctm.2016-007128191785http://onlinelibrary.wiley.com/doi/10.5966/sctm.2016-0071/fullinfo: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:RCAAP2023-07-21T12:47:52Zoai:repositorium.sdum.uminho.pt:1822/49951Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:46:00.110839Repositório 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 |
Impact of the Secretome of Human Mesenchymal Stem Cells on Brain Structure and Animal behavior in a Rat Model of Parkinson’s Disease |
title |
Impact of the Secretome of Human Mesenchymal Stem Cells on Brain Structure and Animal behavior in a Rat Model of Parkinson’s Disease |
spellingShingle |
Impact of the Secretome of Human Mesenchymal Stem Cells on Brain Structure and Animal behavior in a Rat Model of Parkinson’s Disease Teixeira, Fábio Gabriel Rodrigues Mesenchymal stem cells Parkinson ’ s disease Secretome Dopaminergic neurons Neuroprotection Ciências Médicas::Medicina Básica Science & Technology |
title_short |
Impact of the Secretome of Human Mesenchymal Stem Cells on Brain Structure and Animal behavior in a Rat Model of Parkinson’s Disease |
title_full |
Impact of the Secretome of Human Mesenchymal Stem Cells on Brain Structure and Animal behavior in a Rat Model of Parkinson’s Disease |
title_fullStr |
Impact of the Secretome of Human Mesenchymal Stem Cells on Brain Structure and Animal behavior in a Rat Model of Parkinson’s Disease |
title_full_unstemmed |
Impact of the Secretome of Human Mesenchymal Stem Cells on Brain Structure and Animal behavior in a Rat Model of Parkinson’s Disease |
title_sort |
Impact of the Secretome of Human Mesenchymal Stem Cells on Brain Structure and Animal behavior in a Rat Model of Parkinson’s Disease |
author |
Teixeira, Fábio Gabriel Rodrigues |
author_facet |
Teixeira, Fábio Gabriel Rodrigues Carvalho, Miguel M. Panchalingam, K. M. Rodrigues, Ana João Pinheiro, Bárbara Filipa Mendes Anjo, Sandra Manadas, Bruno Behie, Leo A. Sousa, Nuno Salgado, A. J. |
author_role |
author |
author2 |
Carvalho, Miguel M. Panchalingam, K. M. Rodrigues, Ana João Pinheiro, Bárbara Filipa Mendes Anjo, Sandra Manadas, Bruno Behie, Leo A. Sousa, Nuno Salgado, A. J. |
author2_role |
author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Teixeira, Fábio Gabriel Rodrigues Carvalho, Miguel M. Panchalingam, K. M. Rodrigues, Ana João Pinheiro, Bárbara Filipa Mendes Anjo, Sandra Manadas, Bruno Behie, Leo A. Sousa, Nuno Salgado, A. J. |
dc.subject.por.fl_str_mv |
Mesenchymal stem cells Parkinson ’ s disease Secretome Dopaminergic neurons Neuroprotection Ciências Médicas::Medicina Básica Science & Technology |
topic |
Mesenchymal stem cells Parkinson ’ s disease Secretome Dopaminergic neurons Neuroprotection Ciências Médicas::Medicina Básica Science & Technology |
description |
Research in the last decade strongly suggests that mesenchymal stem cell (MSC)-mediated therapeutic benefits are mainly due to their secretome, which has been proposed as a possible therapeutic tool for the treatment of Parkinson's disease (PD). Indeed, it has been shown that the MSC secretome increases neurogenesis and cell survival, and has numerous neuroprotective actions under different conditions. Additionally, using dynamic culturing conditions (through computer-controlled bioreactors) can further modulate the MSC secretome, thereby generating a more potent neurotrophic factor cocktail (i.e., conditioned medium). In this study, we have characterized the MSC secretome by proteomic-based analysis, investigating its therapeutic effects on the physiological recovery of a 6-hydroxidopamine (6-OHDA) PD rat model. For this purpose, we injected MSC secretome into the substantia nigra (SNc) and striatum (STR), characterizing the behavioral performance and determining histological parameters for injected animals versus untreated groups. We observed that the secretome potentiated the increase of dopaminergic neurons (i.e., tyrosine hydroxylase-positive cells) and neuronal terminals in the SNc and STR, respectively, thereby supporting the recovery observed in the Parkinsonian rats' motor performance outcomes (assessed by rotarod and staircase tests). Finally, proteomic characterization of the MSC secretome (through combined mass spectrometry analysis and Bioplex assays) revealed the presence of important neuroregulatory molecules, namely cystatin C, glia-derived nexin, galectin-1, pigment epithelium-derived factor, vascular endothelial growth factor, brain-derived neurotrophic factor, interleukin-6, and glial cell line-derived neurotrophic factor. Overall, we concluded that the use of human MSC secretome alone was able to partially revert the motor phenotype and the neuronal structure of 6-OHDA PD animals. This indicates that the human MSC secretome could represent a novel therapeutic for the treatment of PD. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017 2017-01-01T00:00:00Z |
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/1822/49951 |
url |
http://hdl.handle.net/1822/49951 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Teixeira, F. G., Carvalho, M. M., Panchalingam, K. M., Rodrigues, A. J., Mendes‐Pinheiro, B., Anjo, S., ... & Salgado, A. J. (2017). Impact of the secretome of human mesenchymal stem cells on brain structure and animal behavior in a rat model of Parkinson's disease. Stem cells translational medicine, 6(2), 634-646 2157-6564 2157-6580 10.5966/sctm.2016-0071 28191785 http://onlinelibrary.wiley.com/doi/10.5966/sctm.2016-0071/full |
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 |
Wiley |
publisher.none.fl_str_mv |
Wiley |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799133026622373888 |