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A retinoic acid-enhanced, multicellular human blood-brain barrier model derived from stem cell sources
Blood-brain barrier (BBB) models are often used to investigate BBB function and screen brain-penetrating therapeutics, but it has been difficult to construct a human model that possesses an optimal BBB phenotype and is readily scalable. To address this challenge, we developed a human in vitro BBB mo...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3932448/ https://www.ncbi.nlm.nih.gov/pubmed/24561821 http://dx.doi.org/10.1038/srep04160 |
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author | Lippmann, Ethan S. Al-Ahmad, Abraham Azarin, Samira M. Palecek, Sean P. Shusta, Eric V. |
author_facet | Lippmann, Ethan S. Al-Ahmad, Abraham Azarin, Samira M. Palecek, Sean P. Shusta, Eric V. |
author_sort | Lippmann, Ethan S. |
collection | PubMed |
description | Blood-brain barrier (BBB) models are often used to investigate BBB function and screen brain-penetrating therapeutics, but it has been difficult to construct a human model that possesses an optimal BBB phenotype and is readily scalable. To address this challenge, we developed a human in vitro BBB model comprising brain microvascular endothelial cells (BMECs), pericytes, astrocytes and neurons derived from renewable cell sources. First, retinoic acid (RA) was used to substantially enhance BBB phenotypes in human pluripotent stem cell (hPSC)-derived BMECs, particularly through adherens junction, tight junction, and multidrug resistance protein regulation. RA-treated hPSC-derived BMECs were subsequently co-cultured with primary human brain pericytes and human astrocytes and neurons derived from human neural progenitor cells (NPCs) to yield a fully human BBB model that possessed significant tightness as measured by transendothelial electrical resistance (~5,000 Ωxcm(2)). Overall, this scalable human BBB model may enable a wide range of neuroscience studies. |
format | Online Article Text |
id | pubmed-3932448 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-39324482014-02-26 A retinoic acid-enhanced, multicellular human blood-brain barrier model derived from stem cell sources Lippmann, Ethan S. Al-Ahmad, Abraham Azarin, Samira M. Palecek, Sean P. Shusta, Eric V. Sci Rep Article Blood-brain barrier (BBB) models are often used to investigate BBB function and screen brain-penetrating therapeutics, but it has been difficult to construct a human model that possesses an optimal BBB phenotype and is readily scalable. To address this challenge, we developed a human in vitro BBB model comprising brain microvascular endothelial cells (BMECs), pericytes, astrocytes and neurons derived from renewable cell sources. First, retinoic acid (RA) was used to substantially enhance BBB phenotypes in human pluripotent stem cell (hPSC)-derived BMECs, particularly through adherens junction, tight junction, and multidrug resistance protein regulation. RA-treated hPSC-derived BMECs were subsequently co-cultured with primary human brain pericytes and human astrocytes and neurons derived from human neural progenitor cells (NPCs) to yield a fully human BBB model that possessed significant tightness as measured by transendothelial electrical resistance (~5,000 Ωxcm(2)). Overall, this scalable human BBB model may enable a wide range of neuroscience studies. Nature Publishing Group 2014-02-24 /pmc/articles/PMC3932448/ /pubmed/24561821 http://dx.doi.org/10.1038/srep04160 Text en Copyright © 2014, Macmillan Publishers Limited. All rights reserved http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/ |
spellingShingle | Article Lippmann, Ethan S. Al-Ahmad, Abraham Azarin, Samira M. Palecek, Sean P. Shusta, Eric V. A retinoic acid-enhanced, multicellular human blood-brain barrier model derived from stem cell sources |
title | A retinoic acid-enhanced, multicellular human blood-brain barrier model derived from stem cell sources |
title_full | A retinoic acid-enhanced, multicellular human blood-brain barrier model derived from stem cell sources |
title_fullStr | A retinoic acid-enhanced, multicellular human blood-brain barrier model derived from stem cell sources |
title_full_unstemmed | A retinoic acid-enhanced, multicellular human blood-brain barrier model derived from stem cell sources |
title_short | A retinoic acid-enhanced, multicellular human blood-brain barrier model derived from stem cell sources |
title_sort | retinoic acid-enhanced, multicellular human blood-brain barrier model derived from stem cell sources |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3932448/ https://www.ncbi.nlm.nih.gov/pubmed/24561821 http://dx.doi.org/10.1038/srep04160 |
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