Appropriate human trophoblast lineage specification and differentiation is crucial for the establishment of normal placentation and maintenance of pregnancy. However, due to the lack of proper modeling systems, the molecular mechanisms of these processes are still largely unknown. Much of the early studies in this area have been based on animal models and tumor-derived trophoblast cell lines, both of which are suboptimal for modeling this unique human organ. Recent advances in regenerative and stem cell biology methods have led to development of novel in vitro model systems for studying human trophoblast. These include derivation of human embryonic and induced pluripotent stem cells and establishment of methods for the differentiation of these cells into trophoblast, as well as the more recent derivation of human trophoblast stem cells. In addition, advances in culture conditions, from traditional two-dimensional monolayer culture to 3D culturing systems, have led to development of trophoblast organoid and placenta-on-a-chip model, enabling us to study human trophoblast function in context of more physiologically accurate environment. In this review, we will discuss these various model systems, with a focus on human trophoblast, and their ability to help elucidate the key mechanisms underlying placental development and function. This review focuses on model systems of human trophoblast differentiation, including advantages and limitations of stem cell-based culture, trophoblast organoid, and organ-on-a-chip methods and their applications in understanding placental development and disease.

中文翻译：

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模拟人类滋养层（母胎界面处的胎盘上皮）


适当的人类滋养层谱系规范和分化对于正常胎盘的建立和妊娠的维持至关重要。然而，由于缺乏适当的建模系统，这些过程的分子机制仍然很大程度上未知。该领域的许多早期研究都是基于动物模型和肿瘤来源的滋养层细胞系，这两种细胞对于模拟这种独特的人体器官来说都不是最理想的。再生和干细胞生物学方法的最新进展导致了用于研究人类滋养层的新型体外模型系统的开发。其中包括人胚胎干细胞和诱导多能干细胞的衍生以及这些细胞分化为滋养层的方法的建立，以及最近的人滋养层干细胞的衍生。此外，培养条件的进步，从传统的二维单层培养到3D培养系统，促进了滋养层类器官和胎盘芯片模型的发展，使我们能够在更生理学精确的背景下研究人类滋养层功能。环境。在这篇综述中，我们将讨论这些不同的模型系统，重点关注人类滋养层，以及它们帮助阐明胎盘发育和功能的关键机制的能力。本综述重点关注人类滋养层分化的模型系统，包括基于干细胞的培养、滋养层类器官和芯片上器官方法的优点和局限性及其在了解胎盘发育和疾病方面的应用。