| Download | - View final version: Mouse embryonic stem cell-derived blood–brain barrier model: applicability to studying antibody triggered receptor mediated transcytosis (PDF, 6.0 MiB)
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| DOI | Resolve DOI: https://doi.org/10.1186/s12987-023-00437-0 |
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| Author | Search for: Jezierski, Anna1; Search for: Huang, Jez1; Search for: Haqqani, Arsalan S.1; Search for: Haukenfrers, Julie1; Search for: Liu, Ziying1; Search for: Baumann, Ewa1; Search for: Sodja, Caroline1; Search for: Charlebois, Claudie1; Search for: Delaney, Christie E.1; Search for: Star, Alexandra T.1; Search for: Liu, Qing1; Search for: Stanimirovic, Danica B.1 |
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| Affiliation | - National Research Council Canada. Human Health Therapeutics
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| Format | Text, Article |
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| Subject | blood brain barrier; mouse brain endothelial cells; receptor mediated transcytosis; antibodies; apparent permeability; embryonic stem cells |
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| Abstract | Blood brain barrier (BBB) models in vitro are an important tool to aid in the pre-clinical evaluation and selection of BBB-crossing therapeutics. Stem cell derived BBB models have recently demonstrated a substantial advantage over primary and immortalized brain endothelial cells (BECs) for BBB modeling. Coupled with recent discoveries high-lighting signifcant species diferences in the expression and function of key BBB transporters, the feld is in need of robust, species-specifc BBB models for improved translational predictability. We have developed a mouse BBB model, composed of mouse embryonic stem cell (mESC-D3)-derived brain endothelial-like cells (mBECs), employing a directed monolayer diferentiation strategy. Although the mBECs showed a mixed endothelial-epithelial phenotype, they exhibited high transendothelial electrical resistance, inducible by retinoic acid treatment up to 400 Ω cm² . This tight cell barrier resulted in restricted sodium fuorescein permeability (1.7 × 10⁻⁵ cm/min), signifcantly lower than that of bEnd.3 cells (1.02 × 10⁻³ cm/min) and comparable to human induced pluripotent stem cell (iPSC)-derived BECs (2.0 × 10⁻⁵ cm/min). The mBECs expressed tight junction proteins, polarized and functional P-gp efux transporter and receptor mediated transcytosis (RMT) receptors; collectively important criteria for studying barrier regulation and drug delivery applications in the CNS. In this study, we compared transport of a panel of antibodies binding species selective or cross-reactive epitopes on BBB RMT receptors in both the mBEC and human iPSC-derived BEC model, to demonstrate discrimination of species-specifc BBB transport mechanisms. |
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| Publication date | 2023-05-26 |
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| Publisher | BMC |
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| Licence | |
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| Language | English |
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| Peer reviewed | Yes |
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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 | ffb27f00-65b7-45e8-ae74-1dcdf7bb7f5f |
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| Record created | 2023-08-14 |
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| Record modified | 2023-08-14 |
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