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Establishment of a Human Blood-Brain Barrier Co-culture Model Mimicking the Neurovascular Unit Using Induced Pluri- and Multipotent Stem Cells

Please always quote using this URN: urn:nbn:de:bvb:20-opus-170982
  • 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 transendothelialIn 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 cm\(^{2}\) 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.show moreshow less

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Metadaten
Author: Antje Appelt-Menzel, Alevtina Cubukova, Katharina Günther, Frank Edenhofer, Jörg Piontek, Gerd Krause, Tanja Stüber, Heike Walles, Winfried Neuhaus, Marco Metzger
URN:urn:nbn:de:bvb:20-opus-170982
Document Type:Journal article
Faculties:Medizinische Fakultät / Frauenklinik und Poliklinik
Medizinische Fakultät / Institut für Anatomie und Zellbiologie
Medizinische Fakultät / Lehrstuhl für Tissue Engineering und Regenerative Medizin
Language:English
Parent Title (English):Stem Cell Reports
Year of Completion:2017
Volume:8
Issue:4
Pagenumber:894-906
Source:Stem Cell Reports 2017, 8(4), 894-906. DOI: 10.1016/j.stemcr.2017.02.021
DOI:https://doi.org/10.1016/j.stemcr.2017.02.021
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=28344002
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:blood-brain barrier (BBB) model; human induced pluripotent stem cells (hiPSCs)human induced pluripotent stem cells (hiPSCs); multipotent fetal neural stem cells (fNSCs); neurovascular unit in vitro
Release Date:2019/10/14
Licence (German):License LogoCC BY-NC-ND: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell, Keine Bearbeitungen 4.0 International