Wang Yaqing, Guo Yaqiong, Wang Peng, Liu Jiayue, Zhang Xu, Liu Qian, Wei Lin, Xu Cong, Qin Jianhua
School of Biomedical Engineering, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Suzhou Institute for Advanced Research, University of Science and Technology of China, Suzhou, China.
Commun Biol. 2025 Apr 27;8(1):669. doi: 10.1038/s42003-025-08057-0.
The placenta forms the maternal-fetal interface to protect the developing fetus from xenobiotics or pathogens. However, the understanding of complex placental features and responses to pathogens are hindered due to the lack of near-physiological models. Here, we present an engineered human placental organoid microphysiological system (MPS) incorporated with vascular endothelium, which allows to recapitulate early placental features in a vascular niche. The MPS comprises a customized insert-based organ chip and a rocker, enabling in situ differentiation and formation of placental organoids from human trophoblast stem cells under dynamic culture conditions. By incorporating vascular endothelium, trophoblast organoids (TOs) maintain improved cell viability, long-term trophoblast proliferation and differentiation. Moreover, trophoblast organoids cocultured with endothelium (EndTOs) show the activation of innate immune-related signaling pathways and high-level secretion of distinct immunomodulatory factors, including antiviral type I and III interferons and trophoblast-specific factors. We further demonstrate that EndTOs exhibit attenuated susceptibility to Zika virus (ZIKV) than single cultured TOs, indicating the crucial role of vascular niche in enhancing intrinsic antiviral defenses functions of trophoblasts. This bioinspired placental organoid MPS provides a useful platform for studying placental physiology and relevant diseases.
胎盘形成母胎界面，以保护发育中的胎儿免受外源性物质或病原体的侵害。然而，由于缺乏接近生理状态的模型，对复杂的胎盘特征和对病原体的反应的理解受到了阻碍。在此，我们展示了一种整合了血管内皮的工程化人胎盘类器官微生理系统（MPS），它能够在血管微环境中重现早期胎盘特征。该MPS由定制的基于插入物的器官芯片和摇床组成，能够在动态培养条件下使人滋养层干细胞原位分化并形成胎盘类器官。通过整合血管内皮，滋养层类器官（TOs）保持了更好的细胞活力、长期的滋养层细胞增殖和分化。此外，与内皮细胞共培养的滋养层类器官（EndTOs）显示出先天免疫相关信号通路的激活以及包括抗病毒I型和III型干扰素和滋养层特异性因子在内的多种免疫调节因子的高水平分泌。我们进一步证明，与单一培养的TOs相比，EndTOs对寨卡病毒（ZIKV）的易感性降低，这表明血管微环境在增强滋养层细胞内在抗病毒防御功能中的关键作用。这种受生物启发的胎盘类器官MPS为研究胎盘生理学和相关疾病提供了一个有用的平台。
