Next Article in Journal
Overcoming the Solubility Barrier of Ibuprofen by the Rational Process Design of a Nanocrystal Formulation
Next Article in Special Issue
Blood–Brain Barrier Modulation to Improve Glioma Drug Delivery
Previous Article in Journal
Silver (I) N-Heterocyclic Carbenes Carbosilane Dendritic Systems and Their Imidazolium-Terminated Analogues as Antibacterial Agents: Study of Their Mode of Action
Previous Article in Special Issue
Novel Intrinsic Mechanisms of Active Drug Extrusion at the Blood-Brain Barrier: Potential Targets for Enhancing Drug Delivery to the Brain?
 
 
Article

Non-Human Primate Blood–Brain Barrier and In Vitro Brain Endothelium: From Transcriptome to the Establishment of a New Model

1
Rare and Neurologic Diseases Research Therapeutic Area, Sanofi R&D, 91385 Chilly-Mazarin, France
2
Translational Sciences Unit, Sanofi R&D, 91385 Chilly-Mazarin, France
*
Author to whom correspondence should be addressed.
Pharmaceutics 2020, 12(10), 967; https://doi.org/10.3390/pharmaceutics12100967
Received: 31 August 2020 / Revised: 2 October 2020 / Accepted: 9 October 2020 / Published: 14 October 2020
(This article belongs to the Special Issue New Drug Delivery across the Blood–Brain Barrier)
The non-human primate (NHP)-brain endothelium constitutes an essential alternative to human in the prediction of molecule trafficking across the blood–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 Investig.igated 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. View Full-Text
Keywords: blood–brain barrier; brain endothelial cells; non-human primate; receptor-mediated transcytosis; transcriptomics blood–brain barrier; brain endothelial cells; non-human primate; receptor-mediated transcytosis; transcriptomics
Show Figures

Figure 1

MDPI and ACS Style

Chaves, C.; Do, T.-M.; Cegarra, C.; Roudières, V.; Tolou, S.; Thill, G.; Rocher, C.; Didier, M.; Lesuisse, D. Non-Human Primate Blood–Brain Barrier and In Vitro Brain Endothelium: From Transcriptome to the Establishment of a New Model. Pharmaceutics 2020, 12, 967. https://doi.org/10.3390/pharmaceutics12100967

AMA Style

Chaves C, Do T-M, Cegarra C, Roudières V, Tolou S, Thill G, Rocher C, Didier M, Lesuisse D. Non-Human Primate Blood–Brain Barrier and In Vitro Brain Endothelium: From Transcriptome to the Establishment of a New Model. Pharmaceutics. 2020; 12(10):967. https://doi.org/10.3390/pharmaceutics12100967

Chicago/Turabian Style

Chaves, Catarina, Tuan-Minh Do, Céline Cegarra, Valérie Roudières, Sandrine Tolou, Gilbert Thill, Corinne Rocher, Michel Didier, and Dominique Lesuisse. 2020. "Non-Human Primate Blood–Brain Barrier and In Vitro Brain Endothelium: From Transcriptome to the Establishment of a New Model" Pharmaceutics 12, no. 10: 967. https://doi.org/10.3390/pharmaceutics12100967

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop