Neurodifferentiation and neuroprotection potential of mesenchymal stromal cell-derived secretome produced in different dynamic systems
Autor(a) principal: | |
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Data de Publicação: | 2023 |
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/1822/85619 |
Resumo: | Parkinson’s disease (PD) is the second most common neurodegenerative disorder and is characterized by the degeneration of the dopamine (DA) neurons in the substantia nigra pars compacta, leading to a loss of DA in the basal ganglia. The presence of aggregates of alpha-synuclein (α-synuclein) is seen as the main contributor to the pathogenesis and progression of PD. Evidence suggests that the secretome of mesenchymal stromal cells (MSC) could be a potential cell-free therapy for PD. However, to accelerate the integration of this therapy in the clinical setting, there is still the need to develop a protocol for the large-scale production of secretome under good manufacturing practices (GMP) guidelines. Bioreactors have the capacity to produce large quantities of secretomes in a scalable manner, surpassing the limitations of planar static culture systems. However, few studies focused on the influence of the culture system used to expand MSC, on the secretome composition. In this work, we studied the capacity of the secretome produced by bone marrow-derived mesenchymal stromal cells (BMSC) expanded in a spinner flask (SP) and in a Vertical-Wheel™ bioreactor (VWBR) system, to induce neurodifferentiation of human neural progenitor cells (hNPCs) and to prevent dopaminergic neuron degeneration caused by the overexpression of α-synuclein in one <i>Caenorhabditis elegans</i> model of PD. Results showed that secretomes from both systems were able to induce neurodifferentiation, though the secretome produced in the SP system had a greater effect. Additionally, in the conditions of our study, only the secretome produced in SP had a neuroprotective potential. Lastly, the secretomes had different profiles regarding the presence and/or specific intensity of different molecules, namely, interleukin (IL)-6, IL-4, matrix metalloproteinase-2 (MMP2), and 3 (MMP3), tumor necrosis factor-beta (TNF-β), osteopontin, nerve growth factor beta (NGFβ), granulocyte colony-stimulating factor (GCSF), heparin-binding (HB) epithelial growth factor (EGF)-like growth factor (HB-EGF), and IL-13. Overall, our results suggest that the culture conditions might have influenced the secretory profiles of cultured cells and, consequently, the observed effects. Additional studies should further explore the effects that different culture systems have on the secretome potential of PD. |
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Neurodifferentiation and neuroprotection potential of mesenchymal stromal cell-derived secretome produced in different dynamic systemsBioreactorDynamic systemsMesenchymal stromal cellsParkinson’s diseaseSecretomeParkinson’s disease (PD) is the second most common neurodegenerative disorder and is characterized by the degeneration of the dopamine (DA) neurons in the substantia nigra pars compacta, leading to a loss of DA in the basal ganglia. The presence of aggregates of alpha-synuclein (α-synuclein) is seen as the main contributor to the pathogenesis and progression of PD. Evidence suggests that the secretome of mesenchymal stromal cells (MSC) could be a potential cell-free therapy for PD. However, to accelerate the integration of this therapy in the clinical setting, there is still the need to develop a protocol for the large-scale production of secretome under good manufacturing practices (GMP) guidelines. Bioreactors have the capacity to produce large quantities of secretomes in a scalable manner, surpassing the limitations of planar static culture systems. However, few studies focused on the influence of the culture system used to expand MSC, on the secretome composition. In this work, we studied the capacity of the secretome produced by bone marrow-derived mesenchymal stromal cells (BMSC) expanded in a spinner flask (SP) and in a Vertical-Wheel™ bioreactor (VWBR) system, to induce neurodifferentiation of human neural progenitor cells (hNPCs) and to prevent dopaminergic neuron degeneration caused by the overexpression of α-synuclein in one <i>Caenorhabditis elegans</i> model of PD. Results showed that secretomes from both systems were able to induce neurodifferentiation, though the secretome produced in the SP system had a greater effect. Additionally, in the conditions of our study, only the secretome produced in SP had a neuroprotective potential. Lastly, the secretomes had different profiles regarding the presence and/or specific intensity of different molecules, namely, interleukin (IL)-6, IL-4, matrix metalloproteinase-2 (MMP2), and 3 (MMP3), tumor necrosis factor-beta (TNF-β), osteopontin, nerve growth factor beta (NGFβ), granulocyte colony-stimulating factor (GCSF), heparin-binding (HB) epithelial growth factor (EGF)-like growth factor (HB-EGF), and IL-13. Overall, our results suggest that the culture conditions might have influenced the secretory profiles of cultured cells and, consequently, the observed effects. Additional studies should further explore the effects that different culture systems have on the secretome potential of PD.This work has been funded by la Caixa Foundation and Portuguese Foundation for Science and Technology (FCT) under the agreement LCF/PR/HP20/52300001; ICVS Scientific Microscopy Platform, member of the national infrastructure PPBI—Portuguese Platform of Bioimaging (PPBI-POCI-01-0145-FEDER-022122); by National funds, through the Foundation for Science and Technology (FCT)—project UIDB/50026/2020 and UIDP/50026/2020. CRM was supported by a Ph.D. scholarship from FCT and the company Stemmatters, Biotecnologia e Medicina Regenerativa SA (PD/BDE/127833/2016). Funding received by iBB-Institute for Bioengineering and Biosciences from FCT (UID/BIO/04565/2020) and through the project PTDC/EQU-EQU/31651/2017 is acknowledged. MAF was supported by a Ph.D. scholarship from FCT (SFRH/PD/BD/128328/2017). RC was supported by the EXOpro project (PTDC/EQU-QUE/31651/2017). JPS was supported by a Ph.D. scholarship from FCT and the company Bn’ML—Behavioral & Molecular Lab (PD/BDE/127834/2016). DS was supported by a Ph.D. scholarship from FCT and the company Stemmatters, Biotecnologia e Medicina Regenerativa S.A. (PD/BDE/135567/2018) JC was supported by a Ph.D. scholarship from FCT (SFRH/BD/5813/2020).Multidisciplinary Digital Publishing Institute (MDPI)Universidade do MinhoMarques, Cláudia RaquelFuzeta, Miguel de AlmeidaCunha, Raquel Medina dos SantosPereira-Sousa, JoanaSilva, DeolindaCampos, Jonas OliveiraTeixeira-Castro, AndreiaSousa, Rui Pedro Romero AmandiFernandes-Platzgummer, AnaSilva, Cláudia L. daSalgado, A. J.2023-04-222023-04-22T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/1822/85619engMarques, C.R.; Fuzeta, M.d.A.; dos Santos Cunha, R.M.; Pereira-Sousa, J.; Silva, D.; Campos, J.; Teixeira-Castro, A.; Sousa, R.A.; Fernandes-Platzgummer, A.; da Silva, C.L.; et al. Neurodifferentiation and Neuroprotection Potential of Mesenchymal Stromal Cell-Derived Secretome Produced in Different Dynamic Systems. Biomedicines 2023, 11, 1240. https://doi.org/10.3390/biomedicines110512402227-905910.3390/biomedicines110512401240https://www.mdpi.com/2227-9059/11/5/1240info: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:RCAAP2023-07-22T01:15:57ZPortal AgregadorONG |
dc.title.none.fl_str_mv |
Neurodifferentiation and neuroprotection potential of mesenchymal stromal cell-derived secretome produced in different dynamic systems |
title |
Neurodifferentiation and neuroprotection potential of mesenchymal stromal cell-derived secretome produced in different dynamic systems |
spellingShingle |
Neurodifferentiation and neuroprotection potential of mesenchymal stromal cell-derived secretome produced in different dynamic systems Marques, Cláudia Raquel Bioreactor Dynamic systems Mesenchymal stromal cells Parkinson’s disease Secretome |
title_short |
Neurodifferentiation and neuroprotection potential of mesenchymal stromal cell-derived secretome produced in different dynamic systems |
title_full |
Neurodifferentiation and neuroprotection potential of mesenchymal stromal cell-derived secretome produced in different dynamic systems |
title_fullStr |
Neurodifferentiation and neuroprotection potential of mesenchymal stromal cell-derived secretome produced in different dynamic systems |
title_full_unstemmed |
Neurodifferentiation and neuroprotection potential of mesenchymal stromal cell-derived secretome produced in different dynamic systems |
title_sort |
Neurodifferentiation and neuroprotection potential of mesenchymal stromal cell-derived secretome produced in different dynamic systems |
author |
Marques, Cláudia Raquel |
author_facet |
Marques, Cláudia Raquel Fuzeta, Miguel de Almeida Cunha, Raquel Medina dos Santos Pereira-Sousa, Joana Silva, Deolinda Campos, Jonas Oliveira Teixeira-Castro, Andreia Sousa, Rui Pedro Romero Amandi Fernandes-Platzgummer, Ana Silva, Cláudia L. da Salgado, A. J. |
author_role |
author |
author2 |
Fuzeta, Miguel de Almeida Cunha, Raquel Medina dos Santos Pereira-Sousa, Joana Silva, Deolinda Campos, Jonas Oliveira Teixeira-Castro, Andreia Sousa, Rui Pedro Romero Amandi Fernandes-Platzgummer, Ana Silva, Cláudia L. da Salgado, A. J. |
author2_role |
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 |
Marques, Cláudia Raquel Fuzeta, Miguel de Almeida Cunha, Raquel Medina dos Santos Pereira-Sousa, Joana Silva, Deolinda Campos, Jonas Oliveira Teixeira-Castro, Andreia Sousa, Rui Pedro Romero Amandi Fernandes-Platzgummer, Ana Silva, Cláudia L. da Salgado, A. J. |
dc.subject.por.fl_str_mv |
Bioreactor Dynamic systems Mesenchymal stromal cells Parkinson’s disease Secretome |
topic |
Bioreactor Dynamic systems Mesenchymal stromal cells Parkinson’s disease Secretome |
description |
Parkinson’s disease (PD) is the second most common neurodegenerative disorder and is characterized by the degeneration of the dopamine (DA) neurons in the substantia nigra pars compacta, leading to a loss of DA in the basal ganglia. The presence of aggregates of alpha-synuclein (α-synuclein) is seen as the main contributor to the pathogenesis and progression of PD. Evidence suggests that the secretome of mesenchymal stromal cells (MSC) could be a potential cell-free therapy for PD. However, to accelerate the integration of this therapy in the clinical setting, there is still the need to develop a protocol for the large-scale production of secretome under good manufacturing practices (GMP) guidelines. Bioreactors have the capacity to produce large quantities of secretomes in a scalable manner, surpassing the limitations of planar static culture systems. However, few studies focused on the influence of the culture system used to expand MSC, on the secretome composition. In this work, we studied the capacity of the secretome produced by bone marrow-derived mesenchymal stromal cells (BMSC) expanded in a spinner flask (SP) and in a Vertical-Wheel™ bioreactor (VWBR) system, to induce neurodifferentiation of human neural progenitor cells (hNPCs) and to prevent dopaminergic neuron degeneration caused by the overexpression of α-synuclein in one <i>Caenorhabditis elegans</i> model of PD. Results showed that secretomes from both systems were able to induce neurodifferentiation, though the secretome produced in the SP system had a greater effect. Additionally, in the conditions of our study, only the secretome produced in SP had a neuroprotective potential. Lastly, the secretomes had different profiles regarding the presence and/or specific intensity of different molecules, namely, interleukin (IL)-6, IL-4, matrix metalloproteinase-2 (MMP2), and 3 (MMP3), tumor necrosis factor-beta (TNF-β), osteopontin, nerve growth factor beta (NGFβ), granulocyte colony-stimulating factor (GCSF), heparin-binding (HB) epithelial growth factor (EGF)-like growth factor (HB-EGF), and IL-13. Overall, our results suggest that the culture conditions might have influenced the secretory profiles of cultured cells and, consequently, the observed effects. Additional studies should further explore the effects that different culture systems have on the secretome potential of PD. |
publishDate |
2023 |
dc.date.none.fl_str_mv |
2023-04-22 2023-04-22T00:00:00Z |
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/1822/85619 |
url |
https://hdl.handle.net/1822/85619 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Marques, C.R.; Fuzeta, M.d.A.; dos Santos Cunha, R.M.; Pereira-Sousa, J.; Silva, D.; Campos, J.; Teixeira-Castro, A.; Sousa, R.A.; Fernandes-Platzgummer, A.; da Silva, C.L.; et al. Neurodifferentiation and Neuroprotection Potential of Mesenchymal Stromal Cell-Derived Secretome Produced in Different Dynamic Systems. Biomedicines 2023, 11, 1240. https://doi.org/10.3390/biomedicines11051240 2227-9059 10.3390/biomedicines11051240 1240 https://www.mdpi.com/2227-9059/11/5/1240 |
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 |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
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repository.mail.fl_str_mv |
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_version_ |
1777303874330165248 |