Placental Drug Transport-on-a-Chip: A Microengineered In Vitro Model of Transporter-Mediated Drug Efflux in the Human Placental Barrier.
Placental Drug Transport-on-a-Chip: A Microengineered In Vitro Model of Transporter-Mediated Drug Efflux in the Human Placental Barrier.
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DOI：
10.1002/adhm.201700786
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发表时间：
2018-01
影响因子：
10
通讯作者：
Huh D
中科院分区：
文献类型：
--
作者：
Blundell C;Yi YS;Ma L;Tess ER;Farrell MJ;Georgescu A;Aleksunes LM;Huh D
目前缺乏关于母体给药对发育中的胎儿的影响的知识是全世界主要的公共卫生问题。预测妊娠期药物安全性的第一个关键步骤是筛选药物化合物穿过胎盘的能力。然而，这种类型的临床前研究受到现有体外和离体模型的有限能力的阻碍，以模拟人体胎盘中的母体-胎儿界面的生理药物转运。在这里，我们证明了利用人类胎盘屏障的微工程模型来模拟和研究药物从母体到胎儿循环的转移的原理证明。使用妊娠期糖尿病药物格列本脲作为模型化合物，我们表明，我们的微生理系统能够重建外排转运蛋白介导的主动运输功能的人胎盘屏障，以限制胎儿暴露于母体给药的药物。我们的数据提供的证据表明，胎盘芯片可以作为一个新的筛选平台，使更准确地预测药物在人类胎盘中的转运。
The current lack of knowledge about the effect of maternally administered drugs on the developing fetus is a major public health concern worldwide. The first critical step towards predicting the safety of medications in pregnancy is to screen drug compounds for their ability to cross the placenta. However, this type of preclinical study has been hampered by the limited capacity of existing in vitro and ex vivo models to mimic physiological drug transport across the maternal-fetal interface in the human placenta. Here we demonstrate the proof-of-principle for utilizing a microengineered model of the human placental barrier to simulate and investigate drug transfer from the maternal to the fetal circulation. Using the gestational diabetes drug glyburide as a model compound, we show that our microphysiological system is capable of reconstituting efflux transporter-mediated active transport function of the human placental barrier to limit fetal exposure to maternally administered drugs. Our data provide evidence that the placenta-on-a-chip may serve as a new screening platform to enable more accurate prediction of drug transport in the human placenta.
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影响因子：
9.8
作者：
Mitchell AA;Gilboa SM;Werler MM;Kelley KE;Louik C;Hernández-Díaz S;National Birth Defects Prevention Study
通讯作者：
National Birth Defects Prevention Study
影响因子：
12.3
作者：
Carpenter AE;Jones TR;Lamprecht MR;Clarke C;Kang IH;Friman O;Guertin DA;Chang JH;Lindquist RA;Moffat J;Golland P;Sabatini DM
通讯作者：
Sabatini DM
影响因子：
3.2
作者：
Lager S;Powell TL
通讯作者：
Powell TL
影响因子：
2.7
作者：
Grigsby PL
通讯作者：
Grigsby PL
影响因子：
7.4
作者：
Chueh, Bor-han;Huh, Dongeun;Takayama, Shuichi
通讯作者：
Takayama, Shuichi