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Development of a three-dimensional, all-human in vitro model of the blood-brain barrier using mono-, co-, and tri-cultivation Transwell models

Hatherell, Kathryn; Couraud, Pierre-Olivier; Romero, Ignacio A.; Weksler, Babette and Pilkington, Geoffrey J. (2011). Development of a three-dimensional, all-human in vitro model of the blood-brain barrier using mono-, co-, and tri-cultivation Transwell models. Journal of neuroscience methods, 199(2) pp. 223–229.

DOI (Digital Object Identifier) Link: http://dx.doi.org/10.1016/j.jneumeth.2011.05.012
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Abstract

In vitro models of the blood-brain barrier (B-BB) generally utilise murine or porcine brain endothelium and rat astrocytes which are commonly grown in foetal calf serum supplemented conditions which modulate cell growth rates. Consequently, results gained from these experimental models can be difficult to extrapolate to the human in vivo situation since they are not of human origin. The proposed in vitro Transwell model of the B-BB is a multi-culture human cell system. It requires reconstruction of the human derived B-BB components in vitro (cerebral microvascular endothelial cells, astrocytes, and brain vascular pericytes) in a three-dimensional (3D) configuration based on Transwell filters. Different cell permutations (mono-, co-, and tri-cultivation) were investigated to find the most effective model in terms of tight junction resistance of the human cerebral microvascular endothelial cells. The B-BB model permutations comprised of human astrocytes (CC-2565 and SC-1810), human brain vascular pericytes (HBVP), and human cerebral microvascular endothelial cells (hCMEC/D3), under human serum supplementation. The models were assessed by trans-endothelial electrical resistance (TEER) measurements using an epithelial voltohmmeter, to validate the tight junction formation between hCMEC/D3 cells. Mono-, co-, and tri-cultivation Transwell models constructed with human brain-derived cells under human serum supplementation demonstrated that co-cultivation of astrocytes with endothelial cells produced the most successful model, as determined by TEER. Pericytes on the other hand improved tight junction formation when co-cultured with endothelial cells but did not improve the model to such an extent when grown in tri-cultivation with astrocytes.

Item Type: Journal Article
Copyright Holders: 2011 Elsevier B. V.
ISSN: 1872-678X
Project Funding Details:
Funded Project NameProject IDFunding Body
Not SetNot SetThe Lord Dowding Fund for Humane Research
Not SetNot SetIsle of Man Anticancer
Not SetNot SetThe Institute of Biomedical and Biomolecular Sciences at the University of Portsmouth
Keywords: blood–brain barrier; human model; Transwell model; human pericytes; hCMEC/D3; trans-endothelial electrical resistance
Academic Unit/Department: Science > Life, Health and Chemical Sciences
Interdisciplinary Research Centre: Biomedical Research Network (BRN)
Item ID: 29827
Depositing User: Ignacio A Romero
Date Deposited: 19 Oct 2011 16:09
Last Modified: 07 Mar 2014 15:06
URI: http://oro.open.ac.uk/id/eprint/29827
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