Preclinical assessment of mesenchymal-stem-cell-based therapies in spinocerebellar ataxia type 3
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | https://hdl.handle.net/1822/77636 |
Resumo: | The low regeneration potential of the central nervous system (CNS) represents a challenge for the development of new therapeutic strategies for neurodegenerative diseases, including spinocerebellar ataxias. Spinocerebellar ataxia type 3 (SCA3)—or Machado–Joseph disease (MJD)—is the most common dominant ataxia, being mainly characterized by motor deficits; however, SCA3/MJD has a complex and heterogeneous pathophysiology, involving many CNS brain regions, contributing to the lack of effective therapies. Mesenchymal stem cells (MSCs) have been proposed as a potential therapeutic tool for CNS disorders. Beyond their differentiation potential, MSCs secrete a broad range of neuroregulatory factors that can promote relevant neuroprotective and immunomodulatory actions in different pathophysiological contexts. The objective of this work was to study the effects of (1) human MSC transplantation and (2) human MSC secretome (CM) administration on disease progression in vivo, using the CMVMJD135 mouse model of SCA3/MJD. Our results showed that a single CM administration was more beneficial than MSC transplantation—particularly in the cerebellum and basal ganglia—while no motor improvement was observed when these cell-based therapeutic approaches were applied in the spinal cord. However, the effects observed were mild and transient, suggesting that continuous or repeated administration would be needed, which should be further tested. |
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Preclinical assessment of mesenchymal-stem-cell-based therapies in spinocerebellar ataxia type 3Human mesenchymal stem cellsSecretomeNeurodegenerationSpinocerebellar ataxia type 3Preclinical trialScience & TechnologyThe low regeneration potential of the central nervous system (CNS) represents a challenge for the development of new therapeutic strategies for neurodegenerative diseases, including spinocerebellar ataxias. Spinocerebellar ataxia type 3 (SCA3)—or Machado–Joseph disease (MJD)—is the most common dominant ataxia, being mainly characterized by motor deficits; however, SCA3/MJD has a complex and heterogeneous pathophysiology, involving many CNS brain regions, contributing to the lack of effective therapies. Mesenchymal stem cells (MSCs) have been proposed as a potential therapeutic tool for CNS disorders. Beyond their differentiation potential, MSCs secrete a broad range of neuroregulatory factors that can promote relevant neuroprotective and immunomodulatory actions in different pathophysiological contexts. The objective of this work was to study the effects of (1) human MSC transplantation and (2) human MSC secretome (CM) administration on disease progression in vivo, using the CMVMJD135 mouse model of SCA3/MJD. Our results showed that a single CM administration was more beneficial than MSC transplantation—particularly in the cerebellum and basal ganglia—while no motor improvement was observed when these cell-based therapeutic approaches were applied in the spinal cord. However, the effects observed were mild and transient, suggesting that continuous or repeated administration would be needed, which should be further tested.This research was funded by the National Ataxia Foundation (NAF) and by Portuguese national funds, through the Foundation for Science and Technology (FCT)—projects UIDB/50026/2020, UIDP/50026/2020, POCI-01-0145-FEDER-029206, and through the Santa Casa Neuroscience Awards (Santa Casa da Misericórdia Lisboa)—project MC-04/17. Additionally, this project was funded by the ICVS Scientific Microscopy Platform, a member of the national infrastructure PPBI—Portuguese Platform of Bioimaging (PPBI-POCI-01-0145-FEDER-022122). S.C.S. received an individual fellowship within the project TUBITAK/0007/2014. The FCT funded individual fellowships to J.S C., A.N.-C., B.M.- P., F.G.T., R.L., S.M., N.A.S., C.S.-C., and S.D.-S. (SFRH/BD/140624/2018, SFRH/BPD/118779/2016, SFRH/BD/120124/2016, SFRH/BPD/118408/2016, PD/BDE/127836/2016, CEECIND/01902/2017, CEECIND/04794/2017, CEECIND/03887/2017, and CEECIND/00685/2020).Multidisciplinary Digital Publishing Institute (MDPI)Universidade do MinhoCorreia, Joana Sofia SilvaCarvalho, Andreia Alexandra NevesPinheiro, Bárbara Filipa MendesPires, Joel PereiraTeixeira, Fábio Gabriel RodriguesLima, Rui Augusto RibeiroMonteiro, Susana Isabel GonçalvesSilva, Nuno André MartinsCunha, Carina Isabel SoaresSerra, Sofia CravinoSilva, Sara Carina DuarteCastro, Andreia Cristiana TeixeiraSalgado, A. J.Maciel, P.2021-11-242021-11-24T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/1822/77636engCorreia, J.S.; Neves-Carvalho, A.; Mendes-Pinheiro, B.; Pires, J.; Teixeira, F.G.; Lima, R.; Monteiro, S.; Silva, N.A.; Soares-Cunha, C.; Serra, S.C.; Duarte-Silva, S.; Teixeira-Castro, A.; Salgado, A.J.; Maciel, P. Preclinical Assessment of Mesenchymal-Stem-Cell-Based Therapies in Spinocerebellar Ataxia Type 3. Biomedicines 2021, 9, 1754. https://doi.org/10.3390/biomedicines91217542227-905910.3390/biomedicines91217541754https://www.mdpi.com/2227-9059/9/12/1754info: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:RCAAP2023-07-21T12:23:59Zoai:repositorium.sdum.uminho.pt:1822/77636Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:17:50.877802Repositório 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 |
Preclinical assessment of mesenchymal-stem-cell-based therapies in spinocerebellar ataxia type 3 |
title |
Preclinical assessment of mesenchymal-stem-cell-based therapies in spinocerebellar ataxia type 3 |
spellingShingle |
Preclinical assessment of mesenchymal-stem-cell-based therapies in spinocerebellar ataxia type 3 Correia, Joana Sofia Silva Human mesenchymal stem cells Secretome Neurodegeneration Spinocerebellar ataxia type 3 Preclinical trial Science & Technology |
title_short |
Preclinical assessment of mesenchymal-stem-cell-based therapies in spinocerebellar ataxia type 3 |
title_full |
Preclinical assessment of mesenchymal-stem-cell-based therapies in spinocerebellar ataxia type 3 |
title_fullStr |
Preclinical assessment of mesenchymal-stem-cell-based therapies in spinocerebellar ataxia type 3 |
title_full_unstemmed |
Preclinical assessment of mesenchymal-stem-cell-based therapies in spinocerebellar ataxia type 3 |
title_sort |
Preclinical assessment of mesenchymal-stem-cell-based therapies in spinocerebellar ataxia type 3 |
author |
Correia, Joana Sofia Silva |
author_facet |
Correia, Joana Sofia Silva Carvalho, Andreia Alexandra Neves Pinheiro, Bárbara Filipa Mendes Pires, Joel Pereira Teixeira, Fábio Gabriel Rodrigues Lima, Rui Augusto Ribeiro Monteiro, Susana Isabel Gonçalves Silva, Nuno André Martins Cunha, Carina Isabel Soares Serra, Sofia Cravino Silva, Sara Carina Duarte Castro, Andreia Cristiana Teixeira Salgado, A. J. Maciel, P. |
author_role |
author |
author2 |
Carvalho, Andreia Alexandra Neves Pinheiro, Bárbara Filipa Mendes Pires, Joel Pereira Teixeira, Fábio Gabriel Rodrigues Lima, Rui Augusto Ribeiro Monteiro, Susana Isabel Gonçalves Silva, Nuno André Martins Cunha, Carina Isabel Soares Serra, Sofia Cravino Silva, Sara Carina Duarte Castro, Andreia Cristiana Teixeira Salgado, A. J. Maciel, P. |
author2_role |
author author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Correia, Joana Sofia Silva Carvalho, Andreia Alexandra Neves Pinheiro, Bárbara Filipa Mendes Pires, Joel Pereira Teixeira, Fábio Gabriel Rodrigues Lima, Rui Augusto Ribeiro Monteiro, Susana Isabel Gonçalves Silva, Nuno André Martins Cunha, Carina Isabel Soares Serra, Sofia Cravino Silva, Sara Carina Duarte Castro, Andreia Cristiana Teixeira Salgado, A. J. Maciel, P. |
dc.subject.por.fl_str_mv |
Human mesenchymal stem cells Secretome Neurodegeneration Spinocerebellar ataxia type 3 Preclinical trial Science & Technology |
topic |
Human mesenchymal stem cells Secretome Neurodegeneration Spinocerebellar ataxia type 3 Preclinical trial Science & Technology |
description |
The low regeneration potential of the central nervous system (CNS) represents a challenge for the development of new therapeutic strategies for neurodegenerative diseases, including spinocerebellar ataxias. Spinocerebellar ataxia type 3 (SCA3)—or Machado–Joseph disease (MJD)—is the most common dominant ataxia, being mainly characterized by motor deficits; however, SCA3/MJD has a complex and heterogeneous pathophysiology, involving many CNS brain regions, contributing to the lack of effective therapies. Mesenchymal stem cells (MSCs) have been proposed as a potential therapeutic tool for CNS disorders. Beyond their differentiation potential, MSCs secrete a broad range of neuroregulatory factors that can promote relevant neuroprotective and immunomodulatory actions in different pathophysiological contexts. The objective of this work was to study the effects of (1) human MSC transplantation and (2) human MSC secretome (CM) administration on disease progression in vivo, using the CMVMJD135 mouse model of SCA3/MJD. Our results showed that a single CM administration was more beneficial than MSC transplantation—particularly in the cerebellum and basal ganglia—while no motor improvement was observed when these cell-based therapeutic approaches were applied in the spinal cord. However, the effects observed were mild and transient, suggesting that continuous or repeated administration would be needed, which should be further tested. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-11-24 2021-11-24T00:00:00Z |
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 |
https://hdl.handle.net/1822/77636 |
url |
https://hdl.handle.net/1822/77636 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Correia, J.S.; Neves-Carvalho, A.; Mendes-Pinheiro, B.; Pires, J.; Teixeira, F.G.; Lima, R.; Monteiro, S.; Silva, N.A.; Soares-Cunha, C.; Serra, S.C.; Duarte-Silva, S.; Teixeira-Castro, A.; Salgado, A.J.; Maciel, P. Preclinical Assessment of Mesenchymal-Stem-Cell-Based Therapies in Spinocerebellar Ataxia Type 3. Biomedicines 2021, 9, 1754. https://doi.org/10.3390/biomedicines9121754 2227-9059 10.3390/biomedicines9121754 1754 https://www.mdpi.com/2227-9059/9/12/1754 |
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 |
Multidisciplinary Digital Publishing Institute (MDPI) |
publisher.none.fl_str_mv |
Multidisciplinary Digital Publishing Institute (MDPI) |
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 |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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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 |
repository.mail.fl_str_mv |
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1799132632119771136 |