Zhou J, Sheridan M A, Tian Y, Dahlgren K J, Messler M, Peng T, Zhao A, Ezashi T, Schulz L C, Ulery B D, Roberts R M, Schust D J
Duke Obstetrics & Gynecology, Duke University School of Medicine, Durham, NC 27710, USA.
Department of Obstetrics, Gynecology, and Women's Health, School of Medicine, 1 Hospital Dr, University of Missouri, Columbia, MO 65212, USA.
iScience. 2025 Feb 25;28(3):112099. doi: 10.1016/j.isci.2025.112099. eCollection 2025 Mar 21.
The development of trophoblast organoids has enabled investigation of placental physiology, disease, and early maternal-fetal interactions during a previously restricted stage of pregnancy. A key shortcoming in existing trophoblast organoid methodologies is the non-physiologic position of the syncytiotrophoblast (STB) within the inner portion of the organoid, which neither recapitulates placental villous morphology nor allows for facile modeling of STB exposure to the endometrium or the contents of the intervillous space. Here, we have successfully established apical-out human trophoblast stem cells (hTSC)-sourced organoids with STB forming on the surface of the organoid. These organoids can also be induced to give rise to the extravillous trophoblast (EVT) lineage, which invades into an extracellular matrix-based hydrogel. Compared to previous methods, our organoids more closely mimic developing human placental architecture, offering a novel platform to study normal and abnormal placental development and to model exposures to pharmaceuticals, pathogens, and environmental factors.
滋养层类器官的发展使得在妊娠之前受限的阶段能够对胎盘生理学、疾病以及早期母婴相互作用进行研究。现有滋养层类器官方法的一个关键缺点是合体滋养层（STB）在类器官内部的非生理性位置，这既不能重现胎盘绒毛形态，也无法方便地模拟STB与子宫内膜或绒毛间隙内容物的接触。在此，我们成功建立了顶端向外的、源自人滋养层干细胞（hTSC）的类器官，其STB在类器官表面形成。这些类器官还可被诱导产生绒毛外滋养层（EVT）谱系，后者可侵入基于细胞外基质的水凝胶中。与之前的方法相比，我们的类器官更紧密地模拟了发育中的人类胎盘结构，为研究正常和异常胎盘发育以及模拟药物、病原体和环境因素暴露提供了一个新平台。
