Multicellular Self-Assembled Spheroidal Model of the Blood Brain Barrier

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 cell...

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Bibliographic Details
Published in:Scientific reports 2013-03, Vol.3 (1), p.1500-1500, Article 1500
Main Authors: Urich, Eduard, Patsch, Christoph, Aigner, Stefan, Graf, Martin, Iacone, Roberto, Freskgård, Per-Ola
Format: Article
Language:English
Subjects:
631/154/433
631/378/1341
631/378/87
692/308/575
Astrocytes
Astrocytes - cytology
Astrocytes - metabolism
Blood-brain barrier
Blood-Brain Barrier - cytology
Blood-Brain Barrier - metabolism
Cell Adhesion
Cell Adhesion Molecules - metabolism
Cells, Cultured
Coculture Techniques
Endothelial cells
Endothelial Cells - cytology
Endothelial Cells - metabolism
Humanities and Social Sciences
Humans
Microvessels - cytology
Models, Biological
multidisciplinary
Neovascularization, Physiologic
Pericytes
Pericytes - cytology
Pericytes - metabolism
Receptors, Cell Surface - metabolism
Science
Spheroids, Cellular - cytology
Spheroids, Cellular - metabolism
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Summary: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep01500