• English
  • Deutsch
  • Log In
    Password Login
    or
  • Research Outputs
  • Projects
  • Researchers
  • Institutes
  • Statistics
Repository logo
Fraunhofer-Gesellschaft
  1. Home
  2. Fraunhofer-Gesellschaft
  3. Artikel
  4. Establishment of a human blood-brain barrier co-culture model mimicking the neurovascular unit using induced pluri- and multipotent stem cells
 
  • Details
  • Full
Options
2017
Journal Article
Titel

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. In this article, Metzger and colleagues present the establishment of physiologically relevant human blood-brain barrier quadruple culture models based on induced pluripotent and multipotent stem cells. The novel model can be used as a powerful tool in pharmaceutical drug research and ADMET studies, which may allow a more reliable translation of promising drug candidates into clinical application.
Author(s)
Appelt-Menzel, Antje
Cubukova, Alevtina
Günther, Katharina
Edenhofer, Frank
Piontek, Jörg
Fraunhofer-Institut für Silicatforschung ISC
Krause, Gerd
Fraunhofer-Institut für Silicatforschung ISC
Stüber, Tanja
Walles, Heike
Neuhaus, Winfried
Metzger, Marco
Fraunhofer-Institut für Silicatforschung ISC
Zeitschrift
Stem cell reports
Thumbnail Image
DOI
10.1016/j.stemcr.2017.02.021
Externer Link
Externer Link
Language
English
google-scholar
Fraunhofer-Institut für Grenzflächen- und Bioverfahrenstechnik IGB
Fraunhofer-Institut für Silicatforschung ISC
Tags
  • Stammzelle

  • Cookie settings
  • Imprint
  • Privacy policy
  • Api
  • Send Feedback
© 2022