Wnt activation of immortalized brain endothelial cells as a tool for generating a standardized model of the blood brain barrier in vitro

Reproducing the characteristics and the functional responses of the blood–brain barrier (BBB) in vitro represents an important task for the research community, and would be a critical biotechnological breakthrough. Pharm
Reproducing the characteristics and the functional responses of the blood–brain barrier (BBB) in vitro represents an important task for the research community, and would be a critical biotechnological breakthrough. Pharmaceutical and biotechnology industries provide strong demand for inexpensive and easy-to-handle in vitro BBB models to screen novel drug candidates. Recently, it was shown that canonical Wnt signaling is responsible for the induction of the BBB properties in the neonatal brain microvasculature in vivo. In the present study, following on from earlier observations, we have developed a novel model of the BBB in vitro that may be suitable for large scale screening assays. This model is based on immortalized endothelial cell lines derived from murine and human brain, with no need for co-culture with astrocytes. To maintain the BBB endothelial cell properties, the cell lines are cultured in the presence of Wnt3a or drugs that stabilize β-catenin, or they are infected with a transcriptionally active form of β-catenin. Upon these treatments, the cell lines maintain expression of BBB-specific markers, which results in elevated transendothelial electrical resistance and reduced cell permeability. Importantly, these properties are retained for several passages in culture, and they can be reproduced and maintained in different laboratories over time. We conclude that the brain-derived endothelial cell lines that we have investigated gain their specialized characteristics upon activation of the canonical Wnt pathway. This model may be thus suitable to test the BBB permeability to chemicals or large molecular weight proteins, transmigration of inflammatory cells, treatments with cytokines, and genetic manipulation.
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Author:Roberta Paolinelli, Monica Corada, Luca Ferrarini, Kavi Devraj, Cédric Artus, Cathrin Jacqueline Czupalla, Noemi Rudini, Luigi Maddaluno, Eleanna Papa, Britta Engelhardt, Pierre Olivier Couraud, Stefan Liebner, Elisabetta Dejana
URN:urn:nbn:de:hebis:30:3-311497
DOI:http://dx.doi.org/10.1371/journal.pone.0070233
ISSN:1932-6203
Parent Title (English):PLoS One
Publisher:PLoS
Place of publication:Lawrence, Kan.
Document Type:Article
Language:English
Date of Publication (online):2013/08/05
Date of first Publication:2013/08/05
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2013/08/19
Volume:8
Issue:(8):e70233
Pagenumber:11
Note:
Copyright: © 2013 Paolinelli et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
HeBIS PPN:352055278
Institutes:Medizin
Dewey Decimal Classification:610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 3.0

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