title: Multicellular self-assembled spheroidal model of the blood brain barrier.
abstract: The blood brain barrier (BBB) has evolved unique characteristics such as dense coverage of the endothelial cells by pericytes and interactions with astrocytes through perivascular endfeet. We study BBB formation in a 3-dimensional multicellular spheroid system of human primary brain endothelial cells (hpBECs), primary pericytes (hpPs) and primary astrocytes (hpAs). We show for the first time that hpBECs, hpPs and hpAs spontaneously self-organize into a defined multicellular structure which recapitulates the complex arrangement of the individual cell types in the BBB structure. Pericytes play a crucial role mediating the interaction between hpBECs and hpAs. This process is not dependent on a scaffold support demonstrating that formation and cellular architecture of the BBB is intrinsically programmed within each specific cell type. In a matrigel setup the hpBECs, hpPs and hpAs also undergo self-arrangement to form endothelial tube-like structures tightly covered by hpPs and loosely attached hpAs mainly at the junctions.
authors.affiliation: Pharma Research and Early Development, Neuroscience DTA, F. Hoffmann-La Roche Basel, Switzerland.
authors.forename: Eduard
authors.initials: E
authors.lastname: Urich
authors.forename: Christoph
authors.initials: C
authors.lastname: Patsch
authors.forename: Stefan
authors.initials: S
authors.lastname: Aigner
authors.forename: Martin
authors.initials: M
authors.lastname: Graf
authors.forename: Roberto
authors.initials: R
authors.lastname: Iacone
authors.forename: Per-Ola
authors.initials: PO
authors.lastname: Freskgård
mesh_terms: D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000166:cytology* / Q000378:metabolism; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002478:Cells, Cultured; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D055806:Microvessels / Q000166:cytology; D008954:Models, Biological; D018919:Neovascularization, Physiologic; D020286:Pericytes / Q000166:cytology / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D018874:Spheroids, Cellular / Q000166:cytology* / Q000378:metabolism
chemical_list: D015815:Cell Adhesion Molecules; D011956:Receptors, Cell Surface