title: Stem Cell-Based Human Blood-Brain Barrier Models for Drug Discovery and Delivery.
abstract: The development of novel neuropharmaceuticals requires the evaluation of blood-brain barrier (BBB) permeability and toxicity. Recent studies have highlighted differences in the BBB among different species, with the most important differences involving the expression of P-glycoprotein (P-gp), multidrug resistance-associated proteins, transporters, and claudins. In addition, functional studies have shown that brain pharmacokinetics of P-glycoprotein substrates are different in humans and rodents. Therefore, human BBB models may be an important platform for initial drug screening before in vivo studies. This strategy might help to reduce costs in drug development and failures in clinical studies. We review the differences in the BBB among species, recent advances in the generation of human BBB models, and their applications in drug discovery and delivery.
authors.affiliation: Center of Neurosciences and Cell Biology (CNC), University of Coimbra, 3004-517 Coimbra, Portugal; Center of Innovation in Biotechnology (Biocant), 3060-197 Cantanhede, Portugal; Institute for Interdisciplinary Research, University of Coimbra (IIIUC), 3030-789 Coimbra, Portugal.
authors.forename: S
authors.initials: S
authors.lastname: Aday
authors.affiliation: Blood-Brain Barrier Laboratory, Université d'Artois EA 2465, 62307 Lens, France. Electronic address: romeo.cecchelli@univ-artois.fr.
authors.forename: R
authors.initials: R
authors.lastname: Cecchelli
authors.affiliation: Blood-Brain Barrier Laboratory, Université d'Artois EA 2465, 62307 Lens, France.
authors.forename: D
authors.initials: D
authors.lastname: Hallier-Vanuxeem
authors.affiliation: Blood-Brain Barrier Laboratory, Université d'Artois EA 2465, 62307 Lens, France.
authors.forename: M P
authors.initials: MP
authors.lastname: Dehouck
authors.affiliation: Center of Neurosciences and Cell Biology (CNC), University of Coimbra, 3004-517 Coimbra, Portugal; Center of Innovation in Biotechnology (Biocant), 3060-197 Cantanhede, Portugal; Institute for Interdisciplinary Research, University of Coimbra (IIIUC), 3030-789 Coimbra, Portugal. Electronic address: lino@biocant.pt.
authors.forename: L
authors.initials: L
authors.lastname: Ferreira
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D000818:Animals; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D051379:Mice; D008954:Models, Biological; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B
keywords: blood–brain barrier; in vitro models; neurodegenerative diseases; neuropharmaceuticals; stem cells