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Drug Discov Today. 2003 Oct 15;8(20):944-54.

New approaches to in vitro models of blood-brain barrier drug transport.

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Department of Molecular, Biopharmacy and Genetics, Graduate School of Pharmaceutical Sciences and New Industry Creation, Hatchery Center, Tohoku University, Aoba, Aramaki, Aoba-ku, Sendai 980-8578, Japan.


The pharmaceutical industry has been searching for an in vitro blood-brain barrier (BBB) model that preserves in vivo transporter functions in CNS drug discovery and development. The application of conditionally immortalized cell lines derived from transgenic animals harboring temperature-sensitive SV40 large T-antigen gene, is a rational and promising approach to such a workable in vitro BBB model. The established brain capillary endothelial cell lines retain the in vivo transport rate of several compounds and various forms of gene expression. Furthermore, this new approach has enabled the development of stable and reproducible co-culture models with a pericyte cell line and/or an astrocyte cell line.

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