Stem Cell-Based Human Blood-Brain Barrier Models for Drug Discovery and Delivery

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• 作者：S. Adayp>1p>p> ; p>p>2p>p> ; p>p>3p> ; R. Cecchellip>4p>p> ; p>p>romeo.cecchelli@univ-artois.fr" class="auth_mail" title="E-mail the corresponding authorp> ; D. Hallier-Vanuxeemp>4p> ; M.P. Dehouckp>4p> ; L. Ferreirap>1p>p> ; p>p>2p>p> ; p>p>3p>p> ; p>p>lino@biocant.pt" class="auth_mail" title="E-mail the corresponding authorp>
• 关键词：blood&ndash ; brain barrier ; neuropharmaceuticals ; in vitro models ; neurodegenerative diseases ; stem cells
• 刊名：Trends in Biotechnology
• 出版年：2016
• 出版时间：May 2016
• 年：2016
• 卷：34
• 期：5
• 页码：382-393
• 全文大小：2536 K

文摘

The development of novel neuropharmaceuticals requires the evaluation of blood–brain barrier (BBB) permeability and toxicity. Recent studies have highlighted differences in the BBB among different species, with the most important differences involving the expression of P-glycoprotein (P-gp), multidrug resistance-associated proteins, transporters, and claudins. In addition, functional studies have shown that brain pharmacokinetics of P-glycoprotein substrates are different in humans and rodents. Therefore, human BBB models may be an important platform for initial drug screening before in vivo studies. This strategy might help to reduce costs in drug development and failures in clinical studies. We review the differences in the BBB among species, recent advances in the generation of human BBB models, and their applications in drug discovery and delivery.