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• W4386567035 abstract "In order to establish an in vitro model of the human blood-brain barrier (BBB), MDR1-overexpressing human induced pluripotent stem cells (hiPSCs) were generated, and they were differentiated to MDR1-expressing brain microvascular endothelial-like cells (MDR1-expressing hiPS-BMECs). MDR1-expressing hiPS-BMECs monolayers showed good barrier function in terms of tight junction protein expression and trans-epithelial electrical resistance (TEER). In sequential window acquisition of all theoretical fragment ion spectra mass spectrometry (SWATH-MS), MDR1 protein expression was markedly increased in MDR1-expressing hiPS-BMECs, whereas other ABC and SLC transporters showed almost identical expression between MDR1-expressing hiPS-BMECs and mock hiPS-BMECs, suggesting that MDR1 overexpression had little or no knock-on effect on other proteins. The basolateral-to-apical transport of MDR1 substrates, such as quinidine, [3H]digoxin and [3H]vinblastine, was higher than the apical-to-basolateral transport, and the efflux-dominant transport was attenuated by PSC833, an MDR1-specific inhibitor, indicating that MDR1-mediated efflux transport is functional. The robust MDR1 function was also supported by the efflux-dominant transports of [3H]cyclosporin A, loperamide, cetirizine, and verapamil by MDR1-expressing hiPS-BMECs. These results suggest that MDR1-expressing hiPS-BMECs can be used as an in vitro model of the human BBB." @default.
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• W4386567035 date "2023-09-01" @default.
• W4386567035 modified "2023-10-01" @default.
• W4386567035 title "Development and Functional Evaluation of MDR1-Expressing Microvascular Endothelial-Like Cells Derived from Human iPS Cells as an In Vitro Blood-Brain Barrier Model" @default.
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• W4386567035 doi "https://doi.org/10.1016/j.xphs.2023.09.004" @default.
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