Download | - View final version: A novel human induced pluripotent stem cell blood-brain barrier model: applicability to study antibody-triggered receptor-mediated transcytosis (PDF, 2.2 MiB)
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DOI | Resolve DOI: https://doi.org/10.1038/s41598-018-19522-8 |
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Author | Search for: Ribecco-Lutkiewicz, Maria1; Search for: Sodja, Caroline1; Search for: Haukenfrers, Julie1; Search for: Haqqani, Arsalan S.1; Search for: Ly, Dao1; Search for: Zachar, Peter1; Search for: Baumann, Ewa1; Search for: Ball, Marguerite1; Search for: Huang, Jez; Search for: Rukhlova, Marina1; Search for: Martina, Marzia1; Search for: Liu, Qing; Search for: Stanimirovic, Danica1; Search for: Jezierski, Anna1; Search for: Bani-Yaghoub, Mahmud |
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Affiliation | - National Research Council of Canada. Human Health Therapeutics
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Format | Text, Article |
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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. |
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Publication date | 2018-01-30 |
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Publisher | Nature Publishing Group |
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In | |
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Language | English |
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Peer reviewed | Yes |
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NPARC number | 23002774 |
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Export citation | Export as RIS |
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Report a correction | Report a correction (opens in a new tab) |
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Record identifier | d891f0d8-7b5e-4fc6-b321-22e16d6b338a |
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Record created | 2018-02-05 |
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Record modified | 2020-05-30 |
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