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Title: In vitro modeling of the blood-brain barrier

Fabien Gosselet

Artois University, France

Biography

F.Gosselet graduated in Biology and received a PhD in Cancerology (2006). He completed his education at the blood-brain barrier laboratory (BBB-Lab), located in Lens (France), as post-doctoral fellowship. Then, he obtained an assistant Professor position (2008) and is full Professor since 2016. Since 2015, he is director of the BBB-Lab. This lab routinely uses in vitro BBB models for investigating BBB physiology, its role in neurodegenerative diseases (AD/PD, stroke, brain tumor metastasis,…), for improving drug delivery and for providing data in pharmaco-toxicological field and to pharmaceutical companies. The BBB-lab actively contributes to several national/H2020 research programs. To date, FG published more than 40 research articles.

Abstract

The development of novel therapeutical molecules to treat central nervous diseases (CNS) requires the evaluation of blood-brain barrier (BBB) permeability and toxicity. The BBB is located at the endothelial cells (ECs) of the brain microvessels level and is very complex to study in alive animals. Therefore, the development and the use of in vitro models of the BBB is compulsory for initial drug screening before in vivo studies. For this reason, several in vitro BBB models have been developed since the early 90’s consisting to extract and purify ECs from animals. Recently, significant differences in the BBB have been reported among species suggesting that human BBB models must be privileged. During this oral presentation, the last studies related to the development and optimization of human in vitro BBB models will be discussed. In particular, the development and the use of the brain-like endothelial cells (BLECs) developed in my laboratory will be explained. This model consists to isolate CD34+-hematopoietic stem cells from human umbilical cord blood and to differentiate these cells into ECs. Then, these cells are seeded on matrigel-coated inserts before being co-cultured with brain pericytes to acquire the BBB phenotype in few days. The BLECs express tight junctions and transporters typically observed in brain endothelium and maintain expression of most in vivo BBB properties for at least 20 days. The model is very reproducible since it can be generated from stem cells isolated from different donors and in different laboratories. Using the BLECs model, it is thus possible to investigate the role of the BBB in CNS physiology and to predict CNS distribution of proteins, nanoparticles, drugs. Studies relative to cells, viruses or bacteria transmigration can also be performed. Importance of the insert choice, calculation methods, coating wil be discussed.
Audience take away: 
• The blood-brain barrier physiology and localization will be discussed.
• Differences in BBB among species will be shown.
• Strategies to reproduce in vitro the BBB will be presented. Several models of the BBB will be presented and discussed. A focus on human BBB models will be done.
• Audience will have very useful information regarding the good practices when using in vitro models of the BBB to calculate molecules passage/transport through this barrier.
• The importance to use adequate inserts, coating, protocols will be presented.