Evaluation of a human iPSC-derived BBB model for repeated dose toxicity testing with cyclosporine A as model compound

The blood-brain barrier (BBB) is a highly restrictive that preserves central nervous system homeostasis and ensures optimal brain functioning. Using BBB cell assays makes it possible to investigate whether compound likely compromise BBBs functionality, thereby probably resulting in neurotoxicity. Recently, several protocols obtain human brain-like endothelial cells (BLECs) from induced pluripotent stem (iPSCs) have been reported. Within the framework of European MSCA-ITN in3 project, we explored possibility use an iPSC-derived model assess effects repeated dose treatment with chemicals, using Cyclosporine A (CsA) as compound. BLECs were found exhibit important characteristics up 15 days after end differentiation could be used treatment. Although still undergoing transcriptional changes over time, targeted transcriptome analysis (TempO-Seq) indicated time concentration dependent activation ATF4, XBP1, Nrf2 p53 stress response pathways under CsA Taken together, these results demonstrate this models general hold great potential study exposure allowing personalized patient-specific studies future.