1. Non-Human Primate Blood–Brain Barrier and In Vitro Brain Endothelium: From Transcriptome to the Establishment of a New Model
- Author
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Catarina Chaves, Dominique Lesuisse, Corinne Rocher, Michel Didier, Sandrine Tolou, Gilbert Thill, Céline Cegarra, Tuan Minh Do, and Valérie Roudières
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Endothelium ,lcsh:RS1-441 ,Pharmaceutical Science ,brain endothelial cells ,Transferrin receptor ,non-human primate ,Biology ,Blood–brain barrier ,blood–brain barrier ,Article ,lcsh:Pharmacy and materia medica ,Transcriptome ,03 medical and health sciences ,transcriptomics ,0302 clinical medicine ,medicine ,Receptor ,030304 developmental biology ,0303 health sciences ,Tight junction ,Isolated brain ,humanities ,Cell biology ,medicine.anatomical_structure ,Transcytosis ,nervous system ,cardiovascular system ,receptor-mediated transcytosis ,030217 neurology & neurosurgery - Abstract
The non-human primate (NHP)-brain endothelium constitutes an essential alternative to human in the prediction of molecule trafficking across the blood&ndash, brain barrier (BBB). This study presents a comparison between the NHP transcriptome of freshly isolated brain microcapillaries and in vitro-selected brain endothelial cells (BECs), focusing on important BBB features, namely tight junctions, receptors mediating transcytosis (RMT), ABC and SLC transporters, given its relevance as an alternative model for the molecule trafficking prediction across the BBB and identification of new brain-specific transport mechanisms. In vitro BECs conserved most of the BBB key elements for barrier integrity and control of molecular trafficking. The function of RMT via the transferrin receptor (TFRC) was characterized in this NHP-BBB model, where both human transferrin and anti-hTFRC antibody showed increased apical-to-basolateral passage in comparison to control molecules. In parallel, eventual BBB-related regional differences were investigated in seven-day in vitro-selected BECs from five brain structures: brainstem, cerebellum, cortex, hippocampus, and striatum. Our analysis retrieved few differences in the brain endothelium across brain regions, suggesting a rather homogeneous BBB function across the brain parenchyma. The presently established NHP-derived BBB model closely mimics the physiological BBB, thus representing a ready-to-use tool for assessment of the penetration of biotherapeutics into the human CNS.
- Published
- 2020
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