Human blood-brain-barrier model for repeated dose toxicity testing
2021
University of Artois, Lens, France
The blood-brain barrier (BBB) is a highly restrictive barrier that preserves central nervous system homeostasis and ensures optimal brain function. BBB cell assays can be used to investigate whether an agent can impair the functionality of the BBB and thereby likely lead to neurotoxicity. Recently, several protocols have been published for deriving human brain-like endothelial cells (BLECs) from induced pluripotent stem cells (iPSCs). Here, the question of whether an iPSC-derived model of the BLEC can be used to evaluate the effects of treatment with repeated doses of chemicals was explored, using cyclosporine A (CsA) as a model compound. BLECs were found to retain important properties of the BBB up to 15 days after the end of differentiation and could be used to assess the effects of treatment with repeated doses. Although BLECs still underwent transcriptional changes over time, targeted transcriptome analysis revealed time- and concentration-dependent activation of stress response pathways under CsA treatment. Taken together, these results show that this iPSC model of the BBB and iPSC models, in general, have great potential for investigating the effects of repeated exposure to chemicals and will enable personalised and patient-specific studies in the future.
Evaluation of a human iPSC-derived BBB model for repeated dose toxicity testing with cyclosporine A as model compound
Maxime Culot
Added on: 02-15-2022
[1] https://www.sciencedirect.com/science/article/pii/S0887233321000370?via%3Dihub
