Oral Presentation ESA-SRB-APEG-NZSE 2022

In vitro 3D models of Developing Placenta (#147)

Georgia Kafer 1
  1. University of the Sunshine Coast, Petrie, QLD, Australia

The human placenta is a transient organ built largely from specialised epithelial cells known as trophoblasts. Aberrations in trophoblast development and function are associated with many placental abnormalities. Our understanding of how different trophoblast aberrations cause placental dysfunction has historically been hampered by a lack of suitable systems to model early human trophoblast development. Twenty years ago, researchers demonstrated that trophoblast cells could be differentiated from human embryonic stem cells (hESCs). Initially, the generation of trophoblast from hESCs attracted considerable debate owing to the tightly held notion that extra-embryonic cells (trophoblast) could not be generated from embryonic cells. Two decades on, work contributed by numerous independent research teams across the world has collectively established that pluripotent stem cells (embryonic and induced (iPSCs)) can be differentiated into trophoblast through manipulation of BMP4, FGF and TGF-β signalling. Pluripotent cells can generate major trophoblast cell types including cytotrophoblast (CTB), syncytiotrophoblast (STB) and extra-villous trophoblast (EVT). In this presentation I will outline the benefits of using a pluripotent cell base for modelling trophoblast biology. I will discuss how trophoblast biology varies when cells are cultured in 2-dimensional vs 3-dimensional (3D) systems. I will further provide an overview of how the 3D culture of trophoblasts into “organoids” can model dynamic features of placental villi including CTB-STB fusion, release of STB aggregates and migration of EVTs. I will finally discuss how placental organoid structures (placentoids) can be used to answer previously untestable placental research questions and some anticipated future directions of placental organoid – or “placentoid” research.