Development of a Human iPSC-Derived Placental Barrier-On-Chip Model

Although recently developed placenta-on-chip systems opened promising perspectivesfor placental barrier modelling, they still lack physiologically relevant trophoblasts andare poorly amenable to high-throughput studies. We aimed to implement humaninduced pluripotent stem cells (hiPSC)-derived trophoblasts into a multi-wellmicrofluidic device to develop a physiologically relevant and scalable placental barriermodel. When cultured in a perfused micro-channel against a collagen-based matrix,hiPSC-derived trophoblasts self-arranged into a 3D structure showing invasivebehaviour, fusogenic and endocrine activities, structural integrity and expressingplacental transporters. RNAseq analysis revealed that the microfluidic 3D environmentboosted expression of genes related to early placental structural development, mainlyinvolved in mechanosensing and cell surface receptor signalling. These resultsdemonstrated the feasibility of generating a differentiated syncytium from hiPSC in amicrofluidic platform. Besides expanding hiPSC-derived trophoblast scope ofapplications, this study constitutes an important resource to improve placental barriermodels and boost research and therapeutics evaluation in pregnancy.