The placenta acts as an interface between the fetus and the expecting mother. Various drugs and environmental pollutants can pass through the human placental barrier and may harm the developing fetus. Currently available in vitro placental barrier models are often inadequate, because they are lacking the functional trophoblast cells. Therefore, we developed and characterized a new human placental model using trophoblast stem cells (TSCs) derived from human induced pluripotent stem cells. Umbilical vein endothelial cells, fibroblast, and TSCs were cocultured using micromesh cell culture technique. These cells formed a tight three-layered structure. This coculture model induced progressive fusion of TSCs and formed a syncytialized epithelium that resembles the in vivo syncytiotrophoblast. Our model allowed the cultured trophoblasts to form microvilli and to reconstitute expression and physiological localization of membrane transport proteins, such as transporter for ATP-binding cassette subfamily B member 1, ATP-binding cassette subfamily C member 3, and glucose transporter-1. Drug permeability assays were performed using five compounds. The results from the permeability assays were comparable to the ones obtained with ex vivo placental models. In conclusion, we developed a novel coculture model mimicking human placenta that provides a useful tool for the studies on transfer of substances between the mother and fetus.

中文翻译：

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基于衍生自人类诱导的多能干细胞的滋养层干细胞的新型人类胎盘屏障模型。

胎盘充当胎儿和准妈妈之间的接口。各种药物和环境污染物可以穿过人的胎盘屏障，并可能损害发育中的胎儿。当前可用的体外胎盘屏障模型通常不足，因为它们缺乏功能性滋养细胞。因此，我们使用衍生自人类诱导的多能干细胞的滋养层干细胞（TSC）开发并表征了新的人类胎盘模型。脐静脉内皮细胞，成纤维细胞和TSC使用微网细胞培养技术进行共培养。这些细胞形成了紧密的三层结构。该共培养模型诱导了TSC的进行性融合，并形成了类似于体内的合体上皮合体滋养细胞。我们的模型允许培养的滋养细胞形成微绒毛，并重建膜转运蛋白的表达和生理定位，例如ATP结合盒亚家族B成员1，ATP结合盒亚家族C成员3和葡萄糖转运蛋白1的转运蛋白。使用五种化合物进行药物渗透性测定。渗透性测定的结果与离体胎盘模型获得的结果相当。总之，我们开发了一种新型的模仿人胎盘的共培养模型，该模型为研究母亲与胎儿之间的物质转移提供了有用的工具。