title: A stable and reproducible human blood-brain barrier model derived from hematopoietic stem cells.
abstract: The human blood brain barrier (BBB) is a selective barrier formed by human brain endothelial cells (hBECs), which is important to ensure adequate neuronal function and protect the central nervous system (CNS) from disease. The development of human in vitro BBB models is thus of utmost importance for drug discovery programs related to CNS diseases. Here, we describe a method to generate a human BBB model using cord blood-derived hematopoietic stem cells. The cells were initially differentiated into ECs followed by the induction of BBB properties by co-culture with pericytes. The brain-like endothelial cells (BLECs) express tight junctions and transporters typically observed in brain endothelium and maintain expression of most in vivo BBB properties for at least 20 days. The model is very reproducible since it can be generated from stem cells isolated from different donors and in different laboratories, and could be used to predict CNS distribution of compounds in human. Finally, we provide evidence that Wnt/β-catenin signaling pathway mediates in part the BBB inductive properties of pericytes.
authors.affiliation: Blood Brain Barrier Laboratory, University of Artois, Lens, France.
authors.forename: Romeo
authors.initials: R
authors.lastname: Cecchelli
authors.affiliation: CNC - Center of Neurosciences and Cell Biology, University of Coimbra, Coimbra, Portugal; Biomaterials and Stem Cell-based Therapeutics Laboratory, Biocant - Center of Innovation in Biotechnology, Cantanhede, Portugal.
authors.forename: Sezin
authors.initials: S
authors.lastname: Aday
authors.affiliation: Blood Brain Barrier Laboratory, University of Artois, Lens, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Sevin
authors.affiliation: CNC - Center of Neurosciences and Cell Biology, University of Coimbra, Coimbra, Portugal; Biomaterials and Stem Cell-based Therapeutics Laboratory, Biocant - Center of Innovation in Biotechnology, Cantanhede, Portugal; Institute for Interdisciplinary Research, University of Coimbra (IIIUC), Coimbra, Portugal.
authors.forename: Catarina
authors.initials: C
authors.lastname: Almeida
authors.affiliation: Blood Brain Barrier Laboratory, University of Artois, Lens, France.
authors.forename: Maxime
authors.initials: M
authors.lastname: Culot
authors.affiliation: Blood Brain Barrier Laboratory, University of Artois, Lens, France.
authors.forename: Lucie
authors.initials: L
authors.lastname: Dehouck
authors.affiliation: Theodor Kocher Institute, University of Bern, Bern, Switzerland.
authors.forename: Caroline
authors.initials: C
authors.lastname: Coisne
authors.affiliation: Theodor Kocher Institute, University of Bern, Bern, Switzerland.
authors.forename: Britta
authors.initials: B
authors.lastname: Engelhardt
authors.affiliation: Blood Brain Barrier Laboratory, University of Artois, Lens, France.
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Dehouck
authors.affiliation: CNC - Center of Neurosciences and Cell Biology, University of Coimbra, Coimbra, Portugal; Biomaterials and Stem Cell-based Therapeutics Laboratory, Biocant - Center of Innovation in Biotechnology, Cantanhede, Portugal.
authors.forename: Lino
authors.initials: L
authors.lastname: Ferreira
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000166:cytology*; D002199:Capillary Permeability; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D015870:Gene Expression; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D008954:Models, Biological; D020286:Pericytes / Q000502:physiology; D015203:Reproducibility of Results; D060449:Wnt Signaling Pathway
chemical_list: D015415:Biomarkers; D015815:Cell Adhesion Molecules; D053823:Hedgehog Proteins; C509239:SHH protein, human