Blood–Brain Barrier Dynamic Device with Uniform Shear Stress Distribution for Microscopy and Permeability Measurements

Choublier, Nina (University of Paris, Paris, France) ; Müller, Yoann (School of Engineering, Architecture and Landscape (hepia), HES-SO // University of Applied Sciences Western Switzerland) ; Gomez Baisac, Loris (School of Engineering, Architecture and Landscape (hepia), HES-SO // University of Applied Sciences Western Switzerland) ; Laedermann, Jeremy (School of Engineering, Architecture and Landscape (hepia), HES-SO // University of Applied Sciences Western Switzerland) ; de Rham, Casimir (School of Engineering, Architecture and Landscape (hepia), HES-SO // University of Applied Sciences Western Switzerland) ; Declèves, Xavier (University of Paris, Paris, France ; Hôpital Cochin, Paris, France) ; Roux, Adrien (School of Engineering, Architecture and Landscape (hepia), HES-SO // University of Applied Sciences Western Switzerland)

Neurology has always been one of the therapeutic areas with higher attrition rates. One of the main difficulties is the presence of the blood–brain barrier (BBB) that restricts access to the brain for major drugs. This low success rate has led to an increasing demand for in vitro tools. The shear stress, which positively affects endothelial cell differentiation by mimicking blood flow, is required for a more physiological in vitro BBB model. We created an innovative device specifically designed for cell culture under shear stress to investigate drug permeability. Our dynamic device encompasses two compartments communicating together via a semi-permeable membrane, on which human cerebral microvascular endothelial (hCMEC/D3) cells were seeded. The fluidic controlled environment ensures a laminar and homogenous flow to culture cells for at least seven days. Cell differentiation was characterized by immunodetection of inter-endothelial junctions directly in the device by confocal microscopy. Finally, we performed permeability assay with lucifer yellow in both static and dynamic conditions in parallel. Our dynamic device is suited to the evaluation of barrier function and the study of drug transport across the BBB, but it could also be used with other human cell types to reproduce intestinal or kidney barriers.


Keywords:
Article Type:
scientifique
Faculty:
Ingénierie et Architecture
School:
HEPIA - Genève
Institute:
inSTI - Institut des Sciences et Technologies industrielles
Date:
2021-06
Pagination:
18 p.
Published in:
Applied Sciences
Numeration (vol. no.):
2021, vol. 11, article no. 5584
DOI:
ISSN:
2076-3417
Appears in Collection:



 Record created 2021-06-29, last modified 2021-06-29

Fulltext:
Download fulltext
PDF

Rate this document:

Rate this document:
1
2
3
 
(Not yet reviewed)