title: In vitro models of the blood-brain barrier: An overview of commonly used brain endothelial cell culture models and guidelines for their use.
abstract: The endothelial cells lining the brain capillaries separate the blood from the brain parenchyma. The endothelial monolayer of the brain capillaries serves both as a crucial interface for exchange of nutrients, gases, and metabolites between blood and brain, and as a barrier for neurotoxic components of plasma and xenobiotics. This "blood-brain barrier" function is a major hindrance for drug uptake into the brain parenchyma. Cell culture models, based on either primary cells or immortalized brain endothelial cell lines, have been developed, in order to facilitate in vitro studies of drug transport to the brain and studies of endothelial cell biology and pathophysiology. In this review, we aim to give an overview of established in vitro blood-brain barrier models with a focus on their validation regarding a set of well-established blood-brain barrier characteristics. As an ideal cell culture model of the blood-brain barrier is yet to be developed, we also aim to give an overview of the advantages and drawbacks of the different models described.
authors: Department of Pharmacy, University of Copenhagen, Denmark.
authors: Hans C
authors: HC
authors: Helms
authors: Institute of Pharmaceutical Science, King's College London, UK.
authors: N Joan
authors: NJ
authors: Abbott
authors: Klinik und Poliklinik für Anästhesiologie, University of Wurzburg, Germany.
authors: Malgorzata
authors: M
authors: Burek
authors: Université d'Artois (UArtois), LBHE, EA 2465, Lens, France.
authors: Romeo
authors: R
authors: Cecchelli
authors: Institut Cochin, INSERM U1016, CNRS UMR8104, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors: Pierre-Olivier
authors: PO
authors: Couraud
authors: Institute of Biophysics, Biological Research Centre, HAS, Szeged, Hungary.
authors: Maria A
authors: MA
authors: Deli
authors: Klinik und Poliklinik für Anästhesiologie, University of Wurzburg, Germany.
authors: Carola
authors: C
authors: Förster
authors: Institute of Biochemistry, University of Muenster, Germany.
authors: Hans J
authors: HJ
authors: Galla
authors: Department of Biological Sciences, The Open University, Walton Hall, Milton Keynes, UK.
authors: Ignacio A
authors: IA
authors: Romero
authors: Department of Chemical and Biological Engineering, University of Wisconsin-Madison, WI, USA.
authors: Eric V
authors: EV
authors: Shusta
authors: Department of Chemical and Biological Engineering, University of Wisconsin-Madison, WI, USA.
authors: Matthew J
authors: MJ
authors: Stebbins
authors: Université d'Artois (UArtois), LBHE, EA 2465, Lens, France.
authors: Elodie
authors: E
authors: Vandenhaute
authors: Division of Hematology and Medical Oncology, Weill Cornell Medical College, NY, USA.
authors: Babette
authors: B
authors: Weksler
authors: Department of Pharmacy, University of Copenhagen, Denmark birger.brodin@sund.ku.dk.
authors: Birger
authors: B
authors: Brodin
mesh_terms: D001812:Blood-Brain Barrier / Q000166:cytology*; D001921:Brain / Q000098:blood supply / Q000166:cytology; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology; D004730:Endothelium, Vascular / Q000166:cytology*; D017408:Guidelines as Topic; D006801:Humans; D008954:Models, Biological
keywords: Blood–brain barrier; astrocytes; endothelium; pericytes; stem cells