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

Ken Ichi Hosoya, Satoko Hori, Sumio Ohtsuki, Tetsuya Terasaki

Research output: Contribution to journalReview articlepeer-review

23 Citations (Scopus)

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°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 transport, BCSFB transporters, and the regulation of BCSFB functions.

Original languageEnglish
Pages (from-to)1875-1885
Number of pages11
JournalAdvanced Drug Delivery Reviews
Volume56
Issue number12
DOIs
Publication statusPublished - 2004 Oct 14
Externally publishedYes

Keywords

  • Choroid plexus epithelial cell
  • Immortalized cell line
  • System A
  • Temperature-sensitive SV40 large T-antigen
  • oatp3

ASJC Scopus subject areas

  • Pharmaceutical Science

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