A stable and reproducible human blood-brain barrier model derived from hematopoietic stem cells
Autor(a) principal: | |
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Data de Publicação: | 2014 |
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/10316/109639 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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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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7160 |
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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 |
|
_version_ |
1817552191669403648 |