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  4. Establishment of a human blood-brain barrier co-culture model mimicking the neurovascular unit using induced pluri- and multipotent stem cells
 
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2017
Journal Article
Title

Establishment of a human blood-brain barrier co-culture model mimicking the neurovascular unit using induced pluri- and multipotent stem cells

Abstract
In vitro models of the human blood-brain barrier (BBB) are highly desirable for drug development. This study aims to analyze a set of ten different BBB culture models based on primary cells, human induced pluripotent stem cells (hiPSCs), and multipotent fetal neural stem cells (fNSCs). We systematically investigated the impact of astrocytes, pericytes, and NSCs on hiPSC-derived BBB endothelial cell function and gene expression. The quadruple culture models, based on these four cell types, achieved BBB characteristics including transendothelial electrical resistance (TEER) up to 2,500 Ω cm2 and distinct upregulation of typical BBB genes. A complex in vivo-like tight junction (TJ) network was detected by freeze-fracture and transmission electron microscopy. Treatment with claudin-specific TJ modulators caused TEER decrease, confirming the relevant role of claudin subtypes for paracellular tightness. Drug permeability tests with reference substances were performed and confirmed the suitability of the models for drug transport studies.
Author(s)
Appelt-Menzel, Antje  
Cubukova, Alevtina  
Günther, Katharina
Edenhofer, Frank
Piontek, Jörg
Fraunhofer-Institut für Silicatforschung ISC  
Krause, Gerd
Stüber, Tanja
Fraunhofer-Institut für Silicatforschung ISC  
Walles, Heike  
Neuhaus, Winfried
Metzger, Marco  
Journal
Stem cell reports  
Open Access
DOI
10.1016/j.stemcr.2017.02.021
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Language
English
Fraunhofer-Institut für Grenzflächen- und Bioverfahrenstechnik IGB  
Fraunhofer-Institut für Silicatforschung ISC  
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