关键词: 胎盘, 干细胞, 器官芯片, 类器官, 生殖医学

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 to 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 conventional 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 discuss the limitations and challenges faced by existing placental models in terms of tissue complexity and functional maturity, and look 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