Dr. Maxime Culot is 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 compagnies. For the last decade he has been responsible for pharmaceutical and toxicological applications of cell and tissue culture to CNS drug distribution at the BBB laboratory from Unioversity and Artois and participated in several EU-funded projects (Predict iv; H2020-ITN: BtRAIN; in3; EuroNanomed: DiasYn; H2020-Eurostar: G2B). He is the coordinator of the Master Tox & Ecotox program “MENACE” which focus on New Approach Methodologies (NAMs) and was appointed early 2025 as the Head of the BBB laboratory. His current focus is to study xenobiotics transport across biological barriers using human stem cell derived in vitro models.
Stem cell derived BBB like cells - How likeable are they ?
Abstract :
Human induced pluripotent stem cells (iPSCs) have the capability to generate specific target cell types in vitro and facilitate high-throughput screening of drugs and chemicals at the population level, thus reducing the costs associated with drug discovery and withdrawals post-clinical trials.
In the last decade, multiple protocols for differentiating iPSC-derived blood-brain barrier (BBB) models have been developed. Within the European MSCA-ITN in3 project, the potential of an iPSC-derived BBB model to evaluate the effects of repeated dose chemical treatments was explored. The brain-like endothelial cells (BLECs) exhibited significant BBB characteristics up to 15 days post-differentiation and were utilized to assess the impact of repeated dose treatments.
Although iPSC-derived BBB models and other iPSC-derived models show promise for studying the effects of repeated dose chemical exposure, our research indicates a need for further characterization of these models to enhance their use in toxicological applications. This conclusion was supported by findings that BBB endothelial cells derived from iPSCs continue to undergo transcriptional changes over time following differentiation.
As transcriptomics becomes more cost-effective and single-cell RNA sequencing data of human brain cells become available, it may aid in the characterization of iPSC-derived models. Increased use of transcriptomics is expected to facilitate detailed characterization of current iPSC-BBB models, enabling researchers to develop more relevant human BBB models.