| Téléchargement | - Voir la version finale : Mouse embryonic stem cell-derived blood–brain barrier model: applicability to studying antibody triggered receptor mediated transcytosis (PDF, 6.0 Mio)
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| DOI | Trouver le DOI : https://doi.org/10.1186/s12987-023-00437-0 |
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| Auteur | Rechercher : Jezierski, Anna1; Rechercher : Huang, Jez1; Rechercher : Haqqani, Arsalan S.1; Rechercher : Haukenfrers, Julie1; Rechercher : Liu, Ziying1; Rechercher : Baumann, Ewa1; Rechercher : Sodja, Caroline1; Rechercher : Charlebois, Claudie1; Rechercher : Delaney, Christie E.1; Rechercher : Star, Alexandra T.1; Rechercher : Liu, Qing1; Rechercher : Stanimirovic, Danica B.1 |
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| Affiliation | - Conseil national de recherches Canada. Thérapeutique en santé humaine
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| Format | Texte, Article |
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| Sujet | blood brain barrier; mouse brain endothelial cells; receptor mediated transcytosis; antibodies; apparent permeability; embryonic stem cells |
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| Résumé | 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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| Date de publication | 2023-05-26 |
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| Maison d’édition | BMC |
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| Licence | |
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| Dans | |
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| Langue | anglais |
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| Publications évaluées par des pairs | Oui |
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| Exporter la notice | Exporter en format RIS |
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| Signaler une correction | Signaler une correction (s'ouvre dans un nouvel onglet) |
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| Identificateur de l’enregistrement | ffb27f00-65b7-45e8-ae74-1dcdf7bb7f5f |
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| Enregistrement créé | 2023-08-14 |
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| Enregistrement modifié | 2023-08-14 |
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