Modelling human placental villous development: designing cultures that reflect anatomy

The use of in vitro tools to study trophoblast differentiation and function is essential to improve understanding of normal and abnormal placental development. The relative accessibility of human placentae enables the use of primary trophoblasts and placental explants in a range of in vitro systems. Recent advances in stem cell models, three-dimensional organoid cultures, and organ-on-a-chip systems have further shed light on the complex microenvironment and cell-cell crosstalk involved in placental development. However, understanding each model's strengths and limitations, and which in vivo aspects of human placentation in vitro data acquired does, or does not, accurately reflect, is key to interpret findings appropriately. To help researchers use and design anatomically accurate culture models, this review both outlines our current understanding of placental development, and critically considers the range of established and emerging culture models used to study this, with a focus on those derived from primary tissue.