Assessment of an in vitro transport model using BeWo b30 cells to predict placental transfer of compounds
Assessment of an in vitro transport model using BeWo b30 cells to predict placental transfer of compounds
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DOI：
10.1007/s00204-013-1074-9
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发表时间：
2013-09-01
影响因子：
6.1
通讯作者：
Louisse, Jochem
中科院分区：
文献类型：
--
作者：
Li, Hequn;van Ravenzwaay, Bennard;Louisse, Jochem
人离体胎盘灌注模型已被定期用于研究化合物的经胎盘转运。然而，这种方法是费力的，并且依赖于新鲜人胎盘的存在，阻碍了其用于评估大量化合物。使用BeWo b30细胞的胎盘屏障的体外模型可以提供离体系统的替代方案。本研究旨在评估这种体外模型是否可以用于可靠地预测胎盘转移。为此，将源自人绒毛膜癌的BeWo b30细胞在transwell插入物上生长以形成细胞层，将顶端母体室与基底外侧胎儿室分开。对于一组9种选定的模型化合物，包括参比化合物安替比林，测定了从顶侧室到基底侧室的转运速度。将获得的相对转运速率与文献中报道的离体胎盘灌注研究中获得的这些化合物的转运指数（相对于安替比林转运的量度）进行比较。体外BeWo模型中的相对转运速率与离体模型报告的转运指数具有良好的相关性（R（2）= 0.95）。这表明BeWo模型可能是预测化合物胎盘转移的有价值的体外模型。
The human ex vivo placental perfusion model has regularly been used to study the transplacental transport of compounds. However, this method is laborious and dependent on the presence of fresh human placenta, hampering its use for the assessment of large numbers of compounds. An in vitro model for the placental barrier using BeWo b30 cells may provide an alternative to the ex vivo system. The present study aims to assess whether such an in vitro model could be used to reliably predict placental transfer. To this end, BeWo b30 cells, derived from a human choriocarcinoma, were grown on transwell insert to form a cell layer, separating an apical maternal compartment from a basolateral fetal compartment. For a set of nine selected model compounds, including the reference compound antipyrine, the transport velocity from the apical to the basolateral compartment was determined. Relative transport rates obtained were compared with the transfer indices (a measure for the transport relative to antipyrine) of these compounds obtained in ex vivo placental perfusion studies as reported in the literature. The relative transport rates in the in vitro BeWo model were in good correlation (R (2) = 0.95) with the transfer indices reported for the ex vivo model. This indicates that the BeWo model could be a valuable in vitro model for prediction of placental transfer of compounds.