Current Translational 3D In Vitro Models of Human Placental Tissue

Cellular models of placental tissue have the potential to recapitulate normal physiology, model disease, and facilitate therapeutic drug testing. In vivo or two-dimensional (2D) in vitro models of placental conditions have not been sufficiently representative of whole human tissue, thus have limited physiological relevance. This can be attributed to interspecies differences in placental physiology or a lack of structural complexity. In comparison, three-dimensional (3D) multicellular model systems provide a more sophisticated analogue of human placental tissue. Newer models of human placenta include 3D organoids, placenta-on-a-chip and organoid-on-a-chip, employing a range of materials and methods including pluripotent or trophoblast stem cells, microfluidics and 3D bioprinting. Accurately mimicking in vivo human tissue is crucial to the success of these translational 3D models of the placenta.In turn, a reliable representation of placental tissue architecture will allow discovery of the mechanisms underlying abnormal placental development and inform the prevention, diagnosis and treatment of pregnancy-related disorders such as preeclampsia and fetal growth restriction. Here, we provide a comprehensive critical appraisal of recent advances in 3D placental models, which aim to elucidate placental physiology, development and dysfunction. Additionally, we discuss how these platforms can accelerate the development of better monitoring and treatment strategies for pregnancy complications induced by a dysfunctional placenta.