Abstract
【Purposes】
The blood-brain barrier (BBB) is an important mechanism in central nervous system (CNS) toxicity because it controls the transport of substances between the blood and brain. Therefore, in vitro models of BBB function similar to those in humans are important for the evaluation of CNS toxicity. However, the rarity and weak tight junctions in existing BBB models are problematic. To solve these problems, human iPS cell-derived brain microvascular endothelial cells (iBMECs) with robust tight junction have been developed. But, other functions of iBMECs have not been evaluated, and very few reports have compared drug permeability in iBMECs with that in in vivo models. This study aimed to evaluate iBMECs by comparing the drug permeability between iBMECs and mices or humans.
【Methods】
Expression of genes and proteins related to tight junctions and transporters was analyzed in iBMECs using RT-qPCR and immunofluorescence staining. Drug permeability Papp values were determined through permeability assays. The obtained Papp values were correlated with literature values in in vivo models.
【Results】
iBMECs have robust tight junctions, and the expression of the excretory transporter BCRP was higher compared to human BMECs. Papp values in iBMECs correlated well with those in mices, and correlated well with drug translocation in humans.
【Conclusions】
This study showed a high correlation between drug permeability in iBMECs and in vivo models. Therefore, drug permeation in iBMECs reflects in vivo conditions, which may be applicable to drug permeation prediction and safety assessment.
