A new in vitro model for blood-cerebrospinal fluid barrier transport studies: an immortalized choroid plexus epithelial cell line derived from the tsA58 SV40 large T-antigen gene transgenic rat

Advanced Drug Delivery Reviews
Ken-ichi HosoyaTetsuya Terasaki

Abstract

The blood-cerebrospinal fluid barrier (BCSFB) plays a key role in the influx and efflux transport of drugs and endogenous substrates in the cerebrospinal fluid (CSF). To clarify the molecular mechanism of the BCSFB transport system, a new in vitro BCSFB model, i.e. an immortalized rat choroid plexus epithelial cell line (TR-CSFB), has been established from transgenic rats harboring a temperature-sensitive simian virus 40 large T-antigen gene. TR-CSFB cells grow well at 33 degrees C because of activation of the temperature-sensitive large T-antigen. These cells have a polygonal epithelial cell morphology and express typical choroid plexus epithelial cell markers, such as transthyretin (TTR) and Na+, K+ -ATPase, as well as the transporters, system A and ABCC1/mrp1. The localization of Na+, K+ -ATPase, and the transport direction of system A are polarized in TR-CSFB cells as is the case in vivo. TR-CSFB cells exhibit L-proline and L-glutamic acid uptake activities and may reflect the CSF-to-blood efflux transport functions involving these amino acids in vivo. Using TR-CSFB cells, we found for the first time that oatp3 is expressed at the BCSFB. TR-CSFB cells appear to be a useful in vitro model of the BCSFB for the study of drug t...Continue Reading

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Citations

Nov 14, 2002·International Journal of Pharmaceutics·Ken-ichi HosoyaTetsuya Terasaki
Dec 29, 2007·Cerebrospinal Fluid Research·Joanna Szmydynger-ChodobskaAdam Chodobski
May 26, 2011·Clinical and Experimental Nephrology·Ken-ichi Hosoya, Masanori Tachikawa
Mar 31, 2012·Expert Opinion on Drug Metabolism & Toxicology·Travis T WagerPatrick Trapa
Aug 21, 2013·Drug Metabolism and Pharmacokinetics·Yasuyuki KasaiKen-Ichi Hosoya
Sep 25, 2012·Journal of Neuroscience Methods·Mahamad Yunnus A MahatNarayanan Surendran
Jan 3, 2015·Journal of Neuroscience Methods·Jason K KarimyJ Marc Simard
Aug 31, 2012·The Journal of Pharmacology and Experimental Therapeutics·Masanori TachikawaKen-ichi Hosoya
Nov 2, 2019·Journal of Neuroscience Methods·Ulrike ErbMichael Karremann

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