Towards the Maturation and Characterization of Smooth Muscle Cells Derived from Human Embryonic Stem Cells
Autor(a) principal: | |
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Data de Publicação: | 2011 |
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/10316/15680 https://doi.org/10.1371/journal.pone.0017771 |
Resumo: | In this study we demonstrate that CD34+ cells derived from human embryonic stem cells (hESCs) have higher smooth muscle cell (SMC) potential than CD34− cells. We report that from all inductive signals tested, retinoic acid (RA) and platelet derived growth factor (PDGFBB) are the most effective agents in guiding the differentiation of CD34+ cells into smooth muscle progenitor cells (SMPCs) characterized by the expression of SMC genes and proteins, secretion of SMC-related cytokines, contraction in response to depolarization agents and vasoactive peptides and expression of SMC-related genes in a 3D environment. These cells are also characterized by a low organization of the contractile proteins and the contractility response is mediated by Ca2+, which involves the activation of Rho A/Rho kinase- and Ca2+/calmodulin (CaM)/myosin light chain kinase (MLCK)-dependent pathways. We further show that SMPCs obtained from the differentiation of CD34+ cells with RA, but not with PDGFBB, can be maturated in medium supplemented with endothelin-1 showing at the end individualized contractile filaments. Overall the hESC-derived SMCs presented in this work might be an unlimited source of SMCs for tissue engineering and regenerative medicine. |
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Towards the Maturation and Characterization of Smooth Muscle Cells Derived from Human Embryonic Stem CellsIn this study we demonstrate that CD34+ cells derived from human embryonic stem cells (hESCs) have higher smooth muscle cell (SMC) potential than CD34− cells. We report that from all inductive signals tested, retinoic acid (RA) and platelet derived growth factor (PDGFBB) are the most effective agents in guiding the differentiation of CD34+ cells into smooth muscle progenitor cells (SMPCs) characterized by the expression of SMC genes and proteins, secretion of SMC-related cytokines, contraction in response to depolarization agents and vasoactive peptides and expression of SMC-related genes in a 3D environment. These cells are also characterized by a low organization of the contractile proteins and the contractility response is mediated by Ca2+, which involves the activation of Rho A/Rho kinase- and Ca2+/calmodulin (CaM)/myosin light chain kinase (MLCK)-dependent pathways. We further show that SMPCs obtained from the differentiation of CD34+ cells with RA, but not with PDGFBB, can be maturated in medium supplemented with endothelin-1 showing at the end individualized contractile filaments. Overall the hESC-derived SMCs presented in this work might be an unlimited source of SMCs for tissue engineering and regenerative medicine.Marie Curie-Reintegration GrantMIT-Portugal programCrioestaminalAssociação Viver a CiênciaFundação para a Ciência e a Tecnologia (PTDC/SA-BEB/098468/2008 and PTDC/CTM/099659/2008 to L.F.; SFRH/BD/40077/2007 to H.V.)Public Library of Science2011-03-10info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/15680http://hdl.handle.net/10316/15680https://doi.org/10.1371/journal.pone.0017771engVAZÃO, Helena - Towards the Maturation and Characterization of Smooth Muscle Cells Derived from Human Embryonic Stem Cells. "PLoS ONE". ISSN 1932-6203. 6:3 (2011) e177711932-6203Vazão, HelenaNeves, Ricardo Pires dasGrãos, MárioFerreira, Linoinfo: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:RCAAP2020-05-29T09:42:25Zoai:estudogeral.uc.pt:10316/15680Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:53:33.937420Repositório 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 |
Towards the Maturation and Characterization of Smooth Muscle Cells Derived from Human Embryonic Stem Cells |
title |
Towards the Maturation and Characterization of Smooth Muscle Cells Derived from Human Embryonic Stem Cells |
spellingShingle |
Towards the Maturation and Characterization of Smooth Muscle Cells Derived from Human Embryonic Stem Cells Vazão, Helena |
title_short |
Towards the Maturation and Characterization of Smooth Muscle Cells Derived from Human Embryonic Stem Cells |
title_full |
Towards the Maturation and Characterization of Smooth Muscle Cells Derived from Human Embryonic Stem Cells |
title_fullStr |
Towards the Maturation and Characterization of Smooth Muscle Cells Derived from Human Embryonic Stem Cells |
title_full_unstemmed |
Towards the Maturation and Characterization of Smooth Muscle Cells Derived from Human Embryonic Stem Cells |
title_sort |
Towards the Maturation and Characterization of Smooth Muscle Cells Derived from Human Embryonic Stem Cells |
author |
Vazão, Helena |
author_facet |
Vazão, Helena Neves, Ricardo Pires das Grãos, Mário Ferreira, Lino |
author_role |
author |
author2 |
Neves, Ricardo Pires das Grãos, Mário Ferreira, Lino |
author2_role |
author author author |
dc.contributor.author.fl_str_mv |
Vazão, Helena Neves, Ricardo Pires das Grãos, Mário Ferreira, Lino |
description |
In this study we demonstrate that CD34+ cells derived from human embryonic stem cells (hESCs) have higher smooth muscle cell (SMC) potential than CD34− cells. We report that from all inductive signals tested, retinoic acid (RA) and platelet derived growth factor (PDGFBB) are the most effective agents in guiding the differentiation of CD34+ cells into smooth muscle progenitor cells (SMPCs) characterized by the expression of SMC genes and proteins, secretion of SMC-related cytokines, contraction in response to depolarization agents and vasoactive peptides and expression of SMC-related genes in a 3D environment. These cells are also characterized by a low organization of the contractile proteins and the contractility response is mediated by Ca2+, which involves the activation of Rho A/Rho kinase- and Ca2+/calmodulin (CaM)/myosin light chain kinase (MLCK)-dependent pathways. We further show that SMPCs obtained from the differentiation of CD34+ cells with RA, but not with PDGFBB, can be maturated in medium supplemented with endothelin-1 showing at the end individualized contractile filaments. Overall the hESC-derived SMCs presented in this work might be an unlimited source of SMCs for tissue engineering and regenerative medicine. |
publishDate |
2011 |
dc.date.none.fl_str_mv |
2011-03-10 |
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/10316/15680 http://hdl.handle.net/10316/15680 https://doi.org/10.1371/journal.pone.0017771 |
url |
http://hdl.handle.net/10316/15680 https://doi.org/10.1371/journal.pone.0017771 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
VAZÃO, Helena - Towards the Maturation and Characterization of Smooth Muscle Cells Derived from Human Embryonic Stem Cells. "PLoS ONE". ISSN 1932-6203. 6:3 (2011) e17771 1932-6203 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Public Library of Science |
publisher.none.fl_str_mv |
Public Library of Science |
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 |
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 |
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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1799133822302814208 |