Abstract:

The placenta is an indispensable organ that connects the mother and fetus, playing various roles during pregnancy such as material exchange, hormone secretion, immune regulation, and barrier defense, which are crucial for maintaining normal fetal development. The placental barrier, composed of multiply layers including trophoblasts, basal lamina and fetal capillaries, plays a crucial role in protecting fetus from direct exposure of xenobiotics. Dysfunction of the placenta can lead to various pregnancy complications, such as preeclampsia, fetal growth restriction, and preterm birth, increasing both maternal and fetal morbidity and mortality rates. Although traditional two-dimensional (2D) cell cultures and animal models have been utilized to study placental physiology and pathology, they still have limitations, such as aberrant cell phenotypes and immature functions in 2D cultures as well as inter-species disparities in animal models. Organ-on-a-chip is a microfluidic cell culture device that allows to mimic the tissue microenvironment by control of biochemical signals and dynamic fluid flow, recapitulating the essential structural and functional characteristics of human tissues or organs. It combines bioengineering techniques with biological strategies, holding potential applications in organ development, disease modeling, and drug evaluation. In this review, we outline current progress in placenta-on-a-chip models, focusing on their construction and applications in studying pregnancy-related disorders, developmental toxicity assessment, and maternal-fetal drug transport at the interface. Based on the human placental development process and the features of in vivo tissue microenvironment, we emphasize the design principles and key elements in constructing placenta-on-a-chip models, such as multicellular components, placental barrier, oxygen tension, fluid shear stress, and extracellular matrix microenvironment. We then introduce other engineering strategies including organoids, bioprinting, and hydrogel materials, providing new perspectives for the construction of in vitro biomimetic placental models. We finally discussed the limitations and challenges faced by existing placental models in terms of tissue complexity and functional maturity, and looks ahead to future developments of advanced in vitro placental models to accelerate their applications in the field of reproductive medicine.

Key words: human placenta, stem cell, placenta-on-a-chip, organoid, reproductive medicine

摘要：

胎盘是连接母体与胎儿的重要器官，在孕期发挥着物质交换、激素分泌、免疫调控和屏障防御等多种功能，对维持胎儿正常发育起着关键作用。胎盘功能障碍可能会导致多种妊娠并发症，如先兆子痫、胎儿生长受限和早产等，增加母胎发病率和死亡率。尽管传统的二维细胞培养和动物模型已被用于研究胎盘生理或病理，但仍存在一定局限。器官芯片是一种新型体外模型系统，它将工程学技术与生物学策略相结合，能够在体外模拟人体组织器官的关键结构和功能特点，在组织器官发育、疾病建模和药物评价等方面具有广泛的应用潜力。本文概述了目前胎盘芯片模型的构建及其在妊娠相关疾病、发育毒性评估和母胎界面药物转运等应用中的研究进展。依据人体胎盘发育过程和组织微环境特点，重点介绍了胎盘芯片模型的构筑原理和关键要素，如多细胞组分、胎盘屏障、氧张力、流体剪切力和细胞外基质微环境等，以及其他工程策略包括类器官、生物打印和水凝胶材料等，为实现仿生胎盘模型的体外构建提供了新的思路。讨论了现有胎盘模型在复杂性和功能成熟度等方面面临的局限和挑战，最后展望了未来发展先进的体外胎盘模型并推动其在生殖医学领域的应用前景。

关键词: 胎盘, 干细胞, 器官芯片, 类器官, 生殖医学