A Perfused In Vitro Human iPSC-Derived Blood-Brain Barrier Faithfully Mimics Transferrin Receptor-Mediated Transcytosis of Therapeutic Antibodies.
Biologics
Blood–brain barrier
Induced pluripotent stem cells-derived brain microvascular endothelial cells
Microfluidic system
Receptor-mediated transcytosis
Transferrin receptor
Journal
Cellular and molecular neurobiology
ISSN: 1573-6830
Titre abrégé: Cell Mol Neurobiol
Pays: United States
ID NLM: 8200709
Informations de publication
Date de publication:
Nov 2023
Nov 2023
Historique:
received:
24
04
2023
accepted:
22
08
2023
medline:
27
11
2023
pubmed:
12
9
2023
entrez:
12
9
2023
Statut:
ppublish
Résumé
Delivering biologics to elicit a therapeutic response in the central nervous system (CNS) remains challenging due to the presence of the blood-brain barrier (BBB). Receptor-mediated transcytosis is a strategy to improve brain exposure after systemic drug administration. The availability of a clinically relevant in vitro BBB model is crucial to investigate transcytosis pathways and to predict the penetration of biologics into the CNS. We created a perfused human in vitro BBB model made of induced pluripotent stem cells (iPSC)-derived brain microvascular endothelial cells (BMEC) for studying transferrin receptor-mediated transcytosis. iPSC-derived BMEC were seeded in the top channel of a three-lane microfluidic device (OrganoPlate®). After 2 days in culture, the established cell model exhibited relevant BBB features, including physiological transendothelial electrical resistance in a transwell setting (1500 Ω*cm
Identifiants
pubmed: 37698826
doi: 10.1007/s10571-023-01404-x
pii: 10.1007/s10571-023-01404-x
pmc: PMC10661771
doi:
Substances chimiques
Receptors, Transferrin
0
Antibodies
0
Biological Products
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
4173-4187Informations de copyright
© 2023. The Author(s).
Références
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