Dr. Maxime Culot is a Professor at the Faculty of Sciences, University of Artois, Lens, France,  where he received his Ph.D. in 2007. During his thesis, He participates in a research program with  AstraZeneca aimed at both identifying molecular mechanisms underlying BBB dysfunction in stroke and investigating neurovascular protective actions of various compounds through the use of different in vitro BBB models, proteomics, and cells from knock-out animals. He was also involved in the development of a new in vitro model of the BBB adapted to the screening of large number of compounds and contributed to several research contracts with pharmaceutical companies. In his actual position, he is responsible for pharmaceutical and toxicological applications of cell and tissue culture to CNS drug distribution. Maxime CULOT participated in several EU-funded projects (Predict iv; H2020-ITN: BtRAIN; in3; EuroNanomed: DiasYn; H2020- Eurostar: G2B). 

OpenTox Virtual Conference 2023 

Advanced in vitro models Blood brain barrier models for toxicity testing 

Blood-brain barrier (BBB) cell assays makes it possible to investigate whether a compound is likely to  compromise its functionality, thereby probably resulting in neurotoxicity and to predict CNS  distribution. Recent advances in in vitro modeling of the blood-brain barrier have shown significant  progress in replicating its complex physiological properties. Researchers have achieved more accurate  mimicry of the blood-brain barrier structure and function from human stem cell source using  advanced cell culture techniques, such as co-culturing multiple cell types, incorporating three 

dimensional cultures, and utilizing microfluidic systems. 

Several protocols to obtain human brain-like endothelial cells (BLECs) from induced pluripotent stem  cells (iPSCs) have been reported. Within the framework of the European MSCA-ITN in3 project, we  explored the possibility to use an iPSC-derived BBB model to assess the effects of repeated dose  treatment with chemicals. Our first objective was to evaluate different published protocols to  differentiate iPSCs into BBB like endothelial cells regarding their expression of endothelial markers,  formation of tight barrier and the presence of functional efflux pumps. After some protocol  optimizations, the iPSCs derived BBB cells were found to exhibit important BBB characteristics up to  15 days after the end of the differentiation and could be used to assess the effects of repeated dose  treatment, using Cyclosporine A (CsA) as a model compound. 

Although iPSCs derived BBB cells were still undergoing transcriptional changes over time, a targeted  transcriptome analysis (TempO-Seq) indicated a time and concentration dependent activation of  ATF4, XBP1, Nrf2 and p53 stress response pathways under CsA treatment. 

Taken together, these results demonstrate that this iPSC-derived BBB model and iPSC-derived models  in general hold great potential to study the effects of repeated dose exposure with chemicals, allowing  personalized and patient-specific studies in the future.