A novel human induced pluripotent stem cell blood-brain barrier model: applicability to study antibody-triggered receptor-mediated transcytosis

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DOIResolve DOI: http://doi.org/10.1038/s41598-018-19522-8
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Name affiliation
  1. National Research Council Canada. Human Health Therapeutics
TypeArticle
Journal titleScientific Reports
ISSN2045-2322
Issue8
Article number1873
Abstract
We have developed a renewable, scalable and transgene free human blood-brain barrier model, composed of brain endothelial cells (BECs), generated from human amniotic fluid derived induced pluripotent stem cells (AF-iPSC), which can also give rise to syngeneic neural cells of the neurovascular unit. These AF-iPSC-derived BECs (i-BEC) exhibited high transendothelial electrical resistance (up to 1500 Ω cm2) inducible by astrocyte-derived molecular cues and retinoic acid treatment, polarized expression of functional efflux transporters and receptor mediated transcytosis triggered by antibodies against specific receptors. In vitro human BBB models enable pre-clinical screening of central nervous system (CNS)-targeting drugs and are of particular importance for assessing species-specific/selective transport mechanisms. This i-BEC human BBB model discriminates species-selective antibody- mediated transcytosis mechanisms, is predictive of in vivo CNS exposure of rodent cross-reactive antibodies and can be implemented into pre-clinical CNS drug discovery and development processes.
Publication date
PublisherNature Publishing Group
LanguageEnglish
Peer reviewedYes
NPARC number23002774
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Record identifierd891f0d8-7b5e-4fc6-b321-22e16d6b338a
Record created2018-02-05
Record modified2018-02-05
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