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In Vitro Blood-Brain Barrier Models-An Overview of Established Models and New Microfluidic Approaches.

Wolff, Anette LU ; Antfolk, Maria LU ; Brodin, Birger and Tenje, Maria LU (2015) In Journal of Pharmaceutical Sciences 104(9). p.2727-2746
Abstract
The societal need for new central nervous system (CNS) medicines is substantial, because of the global increase in life expectancy and the accompanying increase in age-related CNS diseases. Low blood-brain barrier (BBB) permeability has been one of the major causes of failure for new CNS drug candidates. There has therefore been a great interest in cell models, which mimic BBB permeation properties. In this review, we present an overview of the performance of monocultured, cocultured, and triple-cultured primary cells and immortalized cell lines, including key parameters such as transendothelial electrical resistance values, permeabilities of paracellular flux markers, and expression of BBB-specific marker proteins. Microfluidic systems... (More)
The societal need for new central nervous system (CNS) medicines is substantial, because of the global increase in life expectancy and the accompanying increase in age-related CNS diseases. Low blood-brain barrier (BBB) permeability has been one of the major causes of failure for new CNS drug candidates. There has therefore been a great interest in cell models, which mimic BBB permeation properties. In this review, we present an overview of the performance of monocultured, cocultured, and triple-cultured primary cells and immortalized cell lines, including key parameters such as transendothelial electrical resistance values, permeabilities of paracellular flux markers, and expression of BBB-specific marker proteins. Microfluidic systems are gaining ground as a new automated technical platform for cell culture and systematic analysis. The performance of these systems was compared with current state-of-the-art models and it was noted that, although they show great promise, these systems have not yet reached beyond the proof-of-concept stage. In general, it was found that there were large variations in experimental protocols, BBB phenotype markers, and paracellular flux markers used. It is the author's opinion that the field may benefit greatly from developing standardized methodologies and initiating collaborative efforts on optimizing culture protocols. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
in
Journal of Pharmaceutical Sciences
volume
104
issue
9
pages
2727 - 2746
publisher
John Wiley & Sons
external identifiers
  • pmid:25630899
  • wos:000359857200007
  • scopus:84939268433
ISSN
0022-3549
DOI
10.1002/jps.24329
language
English
LU publication?
yes
id
096bf564-bab3-4271-bd94-fc8e8384238e (old id 5039303)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/25630899?dopt=Abstract
date added to LUP
2015-02-04 21:28:06
date last changed
2017-11-05 03:20:29
@article{096bf564-bab3-4271-bd94-fc8e8384238e,
  abstract     = {The societal need for new central nervous system (CNS) medicines is substantial, because of the global increase in life expectancy and the accompanying increase in age-related CNS diseases. Low blood-brain barrier (BBB) permeability has been one of the major causes of failure for new CNS drug candidates. There has therefore been a great interest in cell models, which mimic BBB permeation properties. In this review, we present an overview of the performance of monocultured, cocultured, and triple-cultured primary cells and immortalized cell lines, including key parameters such as transendothelial electrical resistance values, permeabilities of paracellular flux markers, and expression of BBB-specific marker proteins. Microfluidic systems are gaining ground as a new automated technical platform for cell culture and systematic analysis. The performance of these systems was compared with current state-of-the-art models and it was noted that, although they show great promise, these systems have not yet reached beyond the proof-of-concept stage. In general, it was found that there were large variations in experimental protocols, BBB phenotype markers, and paracellular flux markers used. It is the author's opinion that the field may benefit greatly from developing standardized methodologies and initiating collaborative efforts on optimizing culture protocols. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci.},
  author       = {Wolff, Anette and Antfolk, Maria and Brodin, Birger and Tenje, Maria},
  issn         = {0022-3549},
  language     = {eng},
  number       = {9},
  pages        = {2727--2746},
  publisher    = {John Wiley & Sons},
  series       = {Journal of Pharmaceutical Sciences},
  title        = {In Vitro Blood-Brain Barrier Models-An Overview of Established Models and New Microfluidic Approaches.},
  url          = {http://dx.doi.org/10.1002/jps.24329},
  volume       = {104},
  year         = {2015},
}