Validation of in vitro cell culture models of the blood–brain barrier: Tightness characterization of two promising cell lines

2008 ◽  
Vol 97 (12) ◽  
pp. 5158-5175 ◽  
Author(s):  
Winfried Neuhaus ◽  
Verena E. Plattner ◽  
Michael Wirth ◽  
Bettina Germann ◽  
Bodo Lachmann ◽  
...  
2016 ◽  
Vol 36 (5) ◽  
pp. 862-890 ◽  
Author(s):  
Hans C Helms ◽  
N Joan Abbott ◽  
Malgorzata Burek ◽  
Romeo Cecchelli ◽  
Pierre-Olivier Couraud ◽  
...  

The endothelial cells lining the brain capillaries separate the blood from the brain parenchyma. The endothelial monolayer of the brain capillaries serves both as a crucial interface for exchange of nutrients, gases, and metabolites between blood and brain, and as a barrier for neurotoxic components of plasma and xenobiotics. This “blood-brain barrier” function is a major hindrance for drug uptake into the brain parenchyma. Cell culture models, based on either primary cells or immortalized brain endothelial cell lines, have been developed, in order to facilitate in vitro studies of drug transport to the brain and studies of endothelial cell biology and pathophysiology. In this review, we aim to give an overview of established in vitro blood–brain barrier models with a focus on their validation regarding a set of well-established blood–brain barrier characteristics. As an ideal cell culture model of the blood–brain barrier is yet to be developed, we also aim to give an overview of the advantages and drawbacks of the different models described.


Stroke ◽  
2014 ◽  
Vol 45 (8) ◽  
pp. 2514-2526 ◽  
Author(s):  
Yarong He ◽  
Yao Yao ◽  
Stella E. Tsirka ◽  
Yu Cao

Neuroscience ◽  
2004 ◽  
Vol 129 (4) ◽  
pp. 935-944 ◽  
Author(s):  
G.P. Nicchia ◽  
B. Nico ◽  
L.M.A. Camassa ◽  
M.G. Mola ◽  
N. Loh ◽  
...  

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Pirmin H. Lakner ◽  
Michael G. Monaghan ◽  
Yvonne Möller ◽  
Monilola A. Olayioye ◽  
Katja Schenke-Layland

2019 ◽  
Author(s):  
Michael M Lübtow ◽  
Sabrina Oertner ◽  
Sabina Quader ◽  
Elisabeth Jeanclos ◽  
Alevtina Cubukova ◽  
...  

Inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase of the family of statins have been suggested as therapeutic options in various tumors. Atorvastatin is a statin with potential to cross the blood-brain-barrier, however, the concentrations necessary for a cytotoxic effect against cancer cells exceeds the concentration achievable via oral administration, which made the development of a novel atorvastatin formulation necessary. We characterized the drug loading and basic physicochemical characteristics of micellar atorvastatin formulations and tested their cytotoxicity against a panel of different glioblastoma cell lines. In addition, activity against tumor spheroids formed from mouse glioma and mouse cancer stem cells, respectively, was evaluated. Our results show good activity of atorvastatin against all tested cell lines. Interestingly, in the 3D models, growth inhibition was more pronounced for the micellar formulation compared to free atorvastatin. Finally, atorvastatin penetration across a blood-brain-barrier model obtained from human induced-pluripotent stem cells was evaluated. Our results suggest that the presented micelles may enable much higher serum concentrations than possible by oral administration, however, if transport across the blood-brain-barrier is sufficient to reach therapeutic atorvastatin concentration for the treatment of glioblastoma via intravenous administration remains unclear.<br>


2014 ◽  
Vol 32 (3) ◽  
pp. 1072-1083 ◽  
Author(s):  
Abdulghani Al-Shehri ◽  
Marco E. Favretto ◽  
Panayiotis V. Ioannou ◽  
Ignacio A. Romero ◽  
Pierre-Olivier Couraud ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document