Division of Biotechnology, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China.
University of Chinese Academy of Sciences, Beijing, China.
Cell Prolif. 2023 May;56(5):e13469. doi: 10.1111/cpr.13469. Epub 2023 May 17.
The placental barrier plays a key role in protecting the developing fetus from xenobiotics and exchanging substances between the fetus and mother. However, the trophoblast cell lines and animal models are often inadequate to recapitulate the key architecture and functional characteristics of human placental barrier. Here, we described a biomimetic placental barrier model from human trophoblast stem cells (hTSCs) in a perfused organ chip system. The placental barrier was constructed by co-culture of hTSCs and endothelial cells on the opposite sides of a collagen-coated membrane on chip. hTSCs can differentiate into cytotrophoblasts (CT) and syncytiotrophoblast (ST), which self-assembled into bilayered trophoblastic epithelium with placental microvilli-like structure under dynamic cultures. The formed placental barrier displayed dense microvilli, higher level secretion of human chorionic gonadotropin (hCG), enhanced glucose transport activity. Moreover, RNA-seq analysis revealed upregulated ST expression and activation of trophoblast differentiation-related signalling pathways. These results indicated the key role of fluid flow in promoting trophoblast syncytialization and placental early development. After exposure to mono-2-ethylhexyl phthalate, one of the endocrine disrupting chemicals, the model showed inhibited hCG production and disturbed ST formation in trophoblastic epithelium, suggesting impaired placental structure and function elicited by environmental toxicants. Collectively, the hTSCs-derived placental model can recapitulate placenta physiology and pathological response to external stimuli in a biomimetic manner, which is useful for the study of placental biology and associated diseases.
胎盘屏障在保护发育中的胎儿免受外源性物质侵害以及在胎儿和母体之间交换物质方面发挥着关键作用。然而，滋养层细胞系和动物模型通常不足以重现人类胎盘屏障的关键结构和功能特征。在这里，我们在灌注式器官芯片系统中描述了一种源自人滋养层干细胞（hTSC）的仿生胎盘屏障模型。胎盘屏障是通过将 hTSC 和内皮细胞共培养在芯片上胶原涂层膜的相对侧构建的。hTSC 可以分化为细胞滋养层（CT）和合体滋养层（ST），在动态培养下，它们自组装成具有胎盘微绒毛样结构的双层滋养层上皮。形成的胎盘屏障显示出密集的微绒毛，人绒毛膜促性腺激素（hCG）的分泌水平更高，葡萄糖转运活性增强。此外，RNA-seq 分析显示 ST 表达上调和滋养层分化相关信号通路激活。这些结果表明，流体流动在促进滋养层合胞体化和胎盘早期发育方面起着关键作用。在暴露于邻苯二甲酸二（2-乙基己基）酯（一种内分泌干扰化学物质）后，该模型显示 hCG 产生受到抑制，滋养层上皮中的 ST 形成受到干扰，表明环境毒物引起胎盘结构和功能受损。总之，源自 hTSC 的胎盘模型可以以仿生方式再现胎盘对外部刺激的生理和病理反应，这对于研究胎盘生物学和相关疾病非常有用。
