Development of a human iPSC-derived placental barrier-on-chip model

Agathe Lermant; Gwenaëlle Rabussier; Henriëtte L Lanz; Lindsay Davidson; Iain M Porter; Colin E Murdoch

doi:10.1016/j.isci.2023.107240

Development of a human iPSC-derived placental barrier-on-chip model

iScience. 2023 Jul 13;26(7):107240. doi: 10.1016/j.isci.2023.107240. eCollection 2023 Jul 21.

Authors

Agathe Lermant¹, Gwenaëlle Rabussier², Henriëtte L Lanz², Lindsay Davidson³, Iain M Porter⁴, Colin E Murdoch¹

Affiliations

¹ Systems Medicine, School of Medicine, University of Dundee, Dundee DD1 9SY, UK.
² MIMETAS, Oegstgeest 2342, the Netherlands.
³ Human Pluripotent Stem Cell Facility, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
⁴ Dundee Imaging Facility, School of Life Sciences, University of Dundee, DD1 5EH, UK.

Abstract

Although recently developed placenta-on-chip systems opened promising perspectives for placental barrier modeling, they still lack physiologically relevant trophoblasts and are poorly amenable to high-throughput studies. We aimed to implement human-induced pluripotent stem cells (hiPSC)-derived trophoblasts into a multi-well microfluidic device to develop a physiologically relevant and scalable placental barrier model. When cultured in a perfused micro-channel against a collagen-based matrix, hiPSC-derived trophoblasts self-arranged into a 3D structure showing invasive behavior, fusogenic and endocrine activities, structural integrity, and expressing placental transporters. RNA-seq analysis revealed that the microfluidic 3D environment boosted expression of genes related to early placental structural development, mainly involved in mechanosensing and cell surface receptor signaling. These results demonstrated the feasibility of generating a differentiated primitive syncytium from hiPSC in a microfluidic platform. Besides expanding hiPSC-derived trophoblast scope of applications, this study constitutes an important resource to improve placental barrier models and boost research and therapeutics evaluation in pregnancy.

Keywords: Biotechnology; Cell biology; Pathophysiology.