Influence of substrates composition on immunomodulation by MSCs

Detalhes bibliográficos
Autor(a) principal: Ferreira, Daniela Filipa Alves
Data de Publicação: 2016
Tipo de documento: Dissertação
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10773/16048
Resumo: Mesenchymal stem cells (MSCs) are non-hematopoietic multipotent stem cells capable to self-renew and differentiate along different cell lineages. MSCs can be found in adult tissues and extra embryonic tissues like the umbilical cord matrix/Wharton’s Jelly (WJ). The latter constitute a good source of MSCs, being more naïve and having a higher proliferative potential than MSCs from adult tissues like the bone marrow, turning them more appealing for clinical use. It is clear that MSCs modulate both innate and adaptive immune responses and its immunodulatory effects are wide, extending to T cells and dendritic cells, being therapeutically useful for treatment of immune system disorders. Mechanotransduction is by definition the mechanism by which cells transform mechanical signals translating that information into biochemical and morphological changes. Here, we hypothesize that by culturing WJ-MSCs on distinct substrates with different stiffness and biochemical composition, may influence the immunomodulatory capacity of the cells. Here, we showed that WJ-MSCs cultured on distinct PDMS substrates presented different secretory profiles from cells cultured on regular tissue culture polystyrene plates (TCP), showing higher secretion of several cytokines analysed. Moreover, it was also shown that WJ-MSCs cultured on PDMS substrates seems to possess higher immunomodulatory capabilities and to differentially regulate the functional compartments of T cells when compared to MSCs maintained on TCP. Taken together, our results suggest that elements of mechanotransduction seem to be influencing the immunomodulatory ability of MSCs, as well as their secretory profile. Thus, future strategies will be further explored to better understand these observation and to envisage new in vitro culture conditions for MSCs aiming at distinct therapeutic approaches, namely for immune-mediated disorders.
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spelling Influence of substrates composition on immunomodulation by MSCsBiomedicina molecularCabeça (Anatomia) - CancroPescoço - CancroCélulas estaminais mesenquimaisMesenchymal stem cells (MSCs) are non-hematopoietic multipotent stem cells capable to self-renew and differentiate along different cell lineages. MSCs can be found in adult tissues and extra embryonic tissues like the umbilical cord matrix/Wharton’s Jelly (WJ). The latter constitute a good source of MSCs, being more naïve and having a higher proliferative potential than MSCs from adult tissues like the bone marrow, turning them more appealing for clinical use. It is clear that MSCs modulate both innate and adaptive immune responses and its immunodulatory effects are wide, extending to T cells and dendritic cells, being therapeutically useful for treatment of immune system disorders. Mechanotransduction is by definition the mechanism by which cells transform mechanical signals translating that information into biochemical and morphological changes. Here, we hypothesize that by culturing WJ-MSCs on distinct substrates with different stiffness and biochemical composition, may influence the immunomodulatory capacity of the cells. Here, we showed that WJ-MSCs cultured on distinct PDMS substrates presented different secretory profiles from cells cultured on regular tissue culture polystyrene plates (TCP), showing higher secretion of several cytokines analysed. Moreover, it was also shown that WJ-MSCs cultured on PDMS substrates seems to possess higher immunomodulatory capabilities and to differentially regulate the functional compartments of T cells when compared to MSCs maintained on TCP. Taken together, our results suggest that elements of mechanotransduction seem to be influencing the immunomodulatory ability of MSCs, as well as their secretory profile. Thus, future strategies will be further explored to better understand these observation and to envisage new in vitro culture conditions for MSCs aiming at distinct therapeutic approaches, namely for immune-mediated disorders.As células estaminais mesenquimais (MSCs) são células não-hematopoéticas, multipotentes, capazes de se auto-renovar e de diferenciar em diferentes tipos celulares. As MSCs estão presentes em tecidos mesenquimais e de tecidos extra embrionários, tais como a matriz do cordão umbilical/Wharton’s Jelly(WJ). Estes últimos constituem uma boa fonte de de MSCs, sendo estas mais naive e tendo um maior potencial de proliferação do que as MSCs obtidas de tecidos adultos, como a medula óssea, tornando as MSCs da matriz do cordão umbilical/Wharton’s Jelly sejam mais apelativas para uso clínico. As MSCs possuem a capacidade de modularem tanto o sistema imune inato como o adquirido e os seus efeitos são vastos, afectando todas as células do sistema imune. Esta capacidade é bastante vantajosa para o uso terapêutico destas células em doenças do sistema imunitário. A mecanotransducção é por definição o mecanismos pelo qual as células convertem estímulos mecânicos em uma resposta bioquímica e com mudanças na sua morfologia. Apartir destas observações colocámos a hipotese de que mantendo MSCs in vitro em diferentes substratos poderia influencia a sua capacidade imunomoduladora. Com este trabalho, demonstrámos que ao plaquear MSCs em diferentes substratos de PDMS, estas mostram uma tendência para secretar quantidades diferentes de vários factores soluveis analisados, relativamente a MSCs mantidas em cultura em plataformas convencionais (placas de cultura de células - TCP). Para além disto, foi também observado que MSCs plaqueadas em substratos de PDMS aparentavam possuir uma maior capacidade imunomoduladora quando comparadas com MSCs mantidas em condições convencionais. Em conjunto todos os resultados obtidos sugerem que elementos relacionados com a mecanotransdução parecem influenciar a capacidade imunomoduladora de MSCs e a sua secreção de factores solúveis. Deste modo, estudos futuros poderão elucidar os mecanismos responsáveis por estas observações, de modo a permitir que se possa constitutuir melhores estratégias de cultura de MSCs para futuro uso terapêutico dirigido a doenças do sistema imunitário.Universidade de Aveiro2018-07-20T14:00:55Z2016-01-06T00:00:00Z2016-01-062017-12-30T12:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/10773/16048TID:201571625engFerreira, Daniela Filipa Alvesinfo: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:RCAAP2024-02-22T11:29:46Zoai:ria.ua.pt:10773/16048Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T02:51:15.783921Repositório 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 Influence of substrates composition on immunomodulation by MSCs
title Influence of substrates composition on immunomodulation by MSCs
spellingShingle Influence of substrates composition on immunomodulation by MSCs
Ferreira, Daniela Filipa Alves
Biomedicina molecular
Cabeça (Anatomia) - Cancro
Pescoço - Cancro
Células estaminais mesenquimais
title_short Influence of substrates composition on immunomodulation by MSCs
title_full Influence of substrates composition on immunomodulation by MSCs
title_fullStr Influence of substrates composition on immunomodulation by MSCs
title_full_unstemmed Influence of substrates composition on immunomodulation by MSCs
title_sort Influence of substrates composition on immunomodulation by MSCs
author Ferreira, Daniela Filipa Alves
author_facet Ferreira, Daniela Filipa Alves
author_role author
dc.contributor.author.fl_str_mv Ferreira, Daniela Filipa Alves
dc.subject.por.fl_str_mv Biomedicina molecular
Cabeça (Anatomia) - Cancro
Pescoço - Cancro
Células estaminais mesenquimais
topic Biomedicina molecular
Cabeça (Anatomia) - Cancro
Pescoço - Cancro
Células estaminais mesenquimais
description Mesenchymal stem cells (MSCs) are non-hematopoietic multipotent stem cells capable to self-renew and differentiate along different cell lineages. MSCs can be found in adult tissues and extra embryonic tissues like the umbilical cord matrix/Wharton’s Jelly (WJ). The latter constitute a good source of MSCs, being more naïve and having a higher proliferative potential than MSCs from adult tissues like the bone marrow, turning them more appealing for clinical use. It is clear that MSCs modulate both innate and adaptive immune responses and its immunodulatory effects are wide, extending to T cells and dendritic cells, being therapeutically useful for treatment of immune system disorders. Mechanotransduction is by definition the mechanism by which cells transform mechanical signals translating that information into biochemical and morphological changes. Here, we hypothesize that by culturing WJ-MSCs on distinct substrates with different stiffness and biochemical composition, may influence the immunomodulatory capacity of the cells. Here, we showed that WJ-MSCs cultured on distinct PDMS substrates presented different secretory profiles from cells cultured on regular tissue culture polystyrene plates (TCP), showing higher secretion of several cytokines analysed. Moreover, it was also shown that WJ-MSCs cultured on PDMS substrates seems to possess higher immunomodulatory capabilities and to differentially regulate the functional compartments of T cells when compared to MSCs maintained on TCP. Taken together, our results suggest that elements of mechanotransduction seem to be influencing the immunomodulatory ability of MSCs, as well as their secretory profile. Thus, future strategies will be further explored to better understand these observation and to envisage new in vitro culture conditions for MSCs aiming at distinct therapeutic approaches, namely for immune-mediated disorders.
publishDate 2016
dc.date.none.fl_str_mv 2016-01-06T00:00:00Z
2016-01-06
2017-12-30T12:00:00Z
2018-07-20T14:00:55Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
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dc.identifier.uri.fl_str_mv http://hdl.handle.net/10773/16048
TID:201571625
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identifier_str_mv TID:201571625
dc.language.iso.fl_str_mv eng
language eng
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 Universidade de Aveiro
publisher.none.fl_str_mv Universidade de Aveiro
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
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collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
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