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 article

22 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

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Transgenic Rats
Polyomavirus Transforming Antigens
Choroid Plexus
Viral Tumor Antigens
Cerebrospinal Fluid
Epithelial Cells
Cell Line
Genes
In Vitro Techniques
Temperature
Prealbumin
Simian virus 40
Proline
Pharmaceutical Preparations
Glutamic Acid
Amino Acids

Keywords

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

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

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. / Hosoya, Ken Ichi; Hori, Satoko; Ohtsuki, Sumio; Terasaki, Tetsuya.

In: Advanced Drug Delivery Reviews, Vol. 56, No. 12, 14.10.2004, p. 1875-1885.

Research output: Contribution to journalReview article

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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.",
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