A stable and reproducible human blood-brain barrier model derived from hematopoietic stem cells.
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...
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Public Library of Science (PLoS)
2014
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oai:doaj.org-article:038b8b5427fb4a6e9883e104b067d9ae2021-11-18T08:15:24ZA stable and reproducible human blood-brain barrier model derived from hematopoietic stem cells.1932-620310.1371/journal.pone.0099733https://doaj.org/article/038b8b5427fb4a6e9883e104b067d9ae2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24936790/?tool=EBIhttps://doaj.org/toc/1932-6203The 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.Romeo CecchelliSezin AdayEmmanuel SevinCatarina AlmeidaMaxime CulotLucie DehouckCaroline CoisneBritta EngelhardtMarie-Pierre DehouckLino FerreiraPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 6, p e99733 (2014) |
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Medicine R Science Q |
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Medicine R Science Q Romeo Cecchelli Sezin Aday Emmanuel Sevin Catarina Almeida Maxime Culot Lucie Dehouck Caroline Coisne Britta Engelhardt Marie-Pierre Dehouck Lino Ferreira A stable and reproducible human blood-brain barrier model derived from hematopoietic stem cells. |
| 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. |
| format |
article |
| author |
Romeo Cecchelli Sezin Aday Emmanuel Sevin Catarina Almeida Maxime Culot Lucie Dehouck Caroline Coisne Britta Engelhardt Marie-Pierre Dehouck Lino Ferreira |
| author_facet |
Romeo Cecchelli Sezin Aday Emmanuel Sevin Catarina Almeida Maxime Culot Lucie Dehouck Caroline Coisne Britta Engelhardt Marie-Pierre Dehouck Lino Ferreira |
| author_sort |
Romeo Cecchelli |
| title |
A stable and reproducible human blood-brain barrier model derived from hematopoietic stem cells. |
| 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 |
stable and reproducible human blood-brain barrier model derived from hematopoietic stem cells. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2014 |
| url |
https://doaj.org/article/038b8b5427fb4a6e9883e104b067d9ae |
| work_keys_str_mv |
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