A stable and reproducible human blood-brain barrier model derived from hematopoietic stem cells

Detalhes bibliográficos
Autor(a) principal: Cecchelli, Romeo
Data de Publicação: 2014
Outros Autores: Aday, Sezin, Sevin, Emmanuel, Almeida, Catarina, Culot, Maxime, Dehouck, Lucie, Coisne, Caroline, Engelhardt, Britta, Dehouck, Marie-Pierre, Ferreira, Lino
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10316/109639
https://doi.org/10.1371/journal.pone.0099733
Resumo: The human blood brain barrier (BBB) is a selective barrier formed by human brain endothelial cells (hBECs), which is important to ensure adequate neuronal function and protect the central nervous system (CNS) from disease. The development of human in vitro BBB models is thus of utmost importance for drug discovery programs related to CNS diseases. Here, we describe a method to generate a human BBB model using cord blood-derived hematopoietic stem cells. The cells were initially differentiated into ECs followed by the induction of BBB properties by co-culture with pericytes. The brain-like endothelial cells (BLECs) express tight junctions and transporters typically observed in brain endothelium and maintain expression of most in vivo BBB properties for at least 20 days. The model is very reproducible since it can be generated from stem cells isolated from different donors and in different laboratories, and could be used to predict CNS distribution of compounds in human. Finally, we provide evidence that Wnt/β-catenin signaling pathway mediates in part the BBB inductive properties of pericytes.
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spelling A stable and reproducible human blood-brain barrier model derived from hematopoietic stem cellsBiomarkersBlood-Brain BarrierCapillary PermeabilityCell Adhesion MoleculesCell DifferentiationCells, CulturedCoculture TechniquesEndothelial CellsEndothelium, VascularGene ExpressionHedgehog ProteinsHematopoietic Stem CellsHumansModels, BiologicalPericytesReproducibility of ResultsWnt Signaling PathwayThe human blood brain barrier (BBB) is a selective barrier formed by human brain endothelial cells (hBECs), which is important to ensure adequate neuronal function and protect the central nervous system (CNS) from disease. The development of human in vitro BBB models is thus of utmost importance for drug discovery programs related to CNS diseases. Here, we describe a method to generate a human BBB model using cord blood-derived hematopoietic stem cells. The cells were initially differentiated into ECs followed by the induction of BBB properties by co-culture with pericytes. The brain-like endothelial cells (BLECs) express tight junctions and transporters typically observed in brain endothelium and maintain expression of most in vivo BBB properties for at least 20 days. The model is very reproducible since it can be generated from stem cells isolated from different donors and in different laboratories, and could be used to predict CNS distribution of compounds in human. Finally, we provide evidence that Wnt/β-catenin signaling pathway mediates in part the BBB inductive properties of pericytes.Public Library of Science2014info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/109639http://hdl.handle.net/10316/109639https://doi.org/10.1371/journal.pone.0099733eng1932-6203Cecchelli, RomeoAday, SezinSevin, EmmanuelAlmeida, CatarinaCulot, MaximeDehouck, LucieCoisne, CarolineEngelhardt, BrittaDehouck, Marie-PierreFerreira, 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:RCAAP2023-10-19T09:30:55Zoai:estudogeral.uc.pt:10316/109639Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:25:47.973791Repositório 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 A stable and reproducible human blood-brain barrier model derived from hematopoietic stem cells
title A stable and reproducible human blood-brain barrier model derived from hematopoietic stem cells
spellingShingle A stable and reproducible human blood-brain barrier model derived from hematopoietic stem cells
Cecchelli, Romeo
Biomarkers
Blood-Brain Barrier
Capillary Permeability
Cell Adhesion Molecules
Cell Differentiation
Cells, Cultured
Coculture Techniques
Endothelial Cells
Endothelium, Vascular
Gene Expression
Hedgehog Proteins
Hematopoietic Stem Cells
Humans
Models, Biological
Pericytes
Reproducibility of Results
Wnt Signaling Pathway
title_short A stable and reproducible human blood-brain barrier model derived from hematopoietic stem cells
title_full A stable and reproducible human blood-brain barrier model derived from hematopoietic stem cells
title_fullStr A stable and reproducible human blood-brain barrier model derived from hematopoietic stem cells
title_full_unstemmed A stable and reproducible human blood-brain barrier model derived from hematopoietic stem cells
title_sort A stable and reproducible human blood-brain barrier model derived from hematopoietic stem cells
author Cecchelli, Romeo
author_facet Cecchelli, Romeo
Aday, Sezin
Sevin, Emmanuel
Almeida, Catarina
Culot, Maxime
Dehouck, Lucie
Coisne, Caroline
Engelhardt, Britta
Dehouck, Marie-Pierre
Ferreira, Lino
author_role author
author2 Aday, Sezin
Sevin, Emmanuel
Almeida, Catarina
Culot, Maxime
Dehouck, Lucie
Coisne, Caroline
Engelhardt, Britta
Dehouck, Marie-Pierre
Ferreira, Lino
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Cecchelli, Romeo
Aday, Sezin
Sevin, Emmanuel
Almeida, Catarina
Culot, Maxime
Dehouck, Lucie
Coisne, Caroline
Engelhardt, Britta
Dehouck, Marie-Pierre
Ferreira, Lino
dc.subject.por.fl_str_mv Biomarkers
Blood-Brain Barrier
Capillary Permeability
Cell Adhesion Molecules
Cell Differentiation
Cells, Cultured
Coculture Techniques
Endothelial Cells
Endothelium, Vascular
Gene Expression
Hedgehog Proteins
Hematopoietic Stem Cells
Humans
Models, Biological
Pericytes
Reproducibility of Results
Wnt Signaling Pathway
topic Biomarkers
Blood-Brain Barrier
Capillary Permeability
Cell Adhesion Molecules
Cell Differentiation
Cells, Cultured
Coculture Techniques
Endothelial Cells
Endothelium, Vascular
Gene Expression
Hedgehog Proteins
Hematopoietic Stem Cells
Humans
Models, Biological
Pericytes
Reproducibility of Results
Wnt Signaling Pathway
description The human blood brain barrier (BBB) is a selective barrier formed by human brain endothelial cells (hBECs), which is important to ensure adequate neuronal function and protect the central nervous system (CNS) from disease. The development of human in vitro BBB models is thus of utmost importance for drug discovery programs related to CNS diseases. Here, we describe a method to generate a human BBB model using cord blood-derived hematopoietic stem cells. The cells were initially differentiated into ECs followed by the induction of BBB properties by co-culture with pericytes. The brain-like endothelial cells (BLECs) express tight junctions and transporters typically observed in brain endothelium and maintain expression of most in vivo BBB properties for at least 20 days. The model is very reproducible since it can be generated from stem cells isolated from different donors and in different laboratories, and could be used to predict CNS distribution of compounds in human. Finally, we provide evidence that Wnt/β-catenin signaling pathway mediates in part the BBB inductive properties of pericytes.
publishDate 2014
dc.date.none.fl_str_mv 2014
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/10316/109639
http://hdl.handle.net/10316/109639
https://doi.org/10.1371/journal.pone.0099733
url http://hdl.handle.net/10316/109639
https://doi.org/10.1371/journal.pone.0099733
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 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
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 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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