Modelling human placental villous development: designing cultures that reflect anatomy

Abstract

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.

Endocrine-disrupting compounds and their impact on human placental function: evidence from placenta organ-on-chip studies

“…19,20 Explants provide a complete structure of the placenta ex vivo; however, temporal differences in the viability of harvested tissue and spatial resolution of individual cells will be tedious and expensive. [95][96][97][98] 2D cultures are the simplest and most costeffective but do not represent the entire organ and cannot replicate intercellular interactions. 99 Conversely, animal models do not necessarily translate into human pregnancy conditions owing to the difference in placentation mechanics and structure.…”

Glycolysis: A fork in the path of normal and pathological pregnancy

“…At ~28 dpf, the basic villous structure consists of a mesenchymal core containing fetal blood vessels, macrophages, pericytes, and connective tissue and an outer layer composed of CTBs and STBs. 44,48,49 The placenta includes floating villi located in the intervillous space and anchoring villi attached to the decidua. CTB division, differentiation, and fusion with the syncytium generate STBs, which cover the surface of the floating villi.…”

“…Shortly thereafter, tertiary villi form when original endothelial tubes develop within the mesenchymal core. At ~28 dpf, the basic villous structure consists of a mesenchymal core containing fetal blood vessels, macrophages, pericytes, and connective tissue and an outer layer composed of CTBs and STBs 44,48,49 . The placenta includes floating villi located in the intervillous space and anchoring villi attached to the decidua.…”

Human-Based New Approach Methodologies in Developmental Toxicity Testing: A Step Ahead from the State of the Art with a Feto–Placental Organ-on-Chip Platform

“…Compared to cell or organoid cultures, placental explants have the advantages of being original primary tissue containing different cell types morphologically assembled as in the in vivo microenvironment and consisting of the typical placental barrier formed by syncytiotrophoblasts, cytotrophoblast cells and the endothelium of the fetal capillaries. Moreover, all surrounding cell types, such as stroma and immune cells, including Hofbauer cells, are preserved and can be investigated in culture over a long time (up to 28 days), although the different cell types have different behavior and viability over time [ 37 ]. After a few days of regeneration, the syncytiotrophoblast re-establishes [ 38 ] and produces hormones such as estradiol, progesterone or β-hCG.…”