Healthy and diseased placenta barrier on-a-chip models suitable for high-throughput studies

Abstract

Preeclampsia is one of the leading causes of maternal and perinatal morbidity in the world. Its fundamental mechanisms are yet poorly understood due to a lack of good experimental models. Here we report an in vitro model of the placental barrier, based on co-culture of trophoblasts and endothelial cells against a collagen extracellular matrix in a microfluidic platform. The model yielded a functional syncytium with barrier properties, polarization, secretion of relevant extracellular membrane components, thinning of the materno-fetal space, hormone secretion, and transporter function. The model was exposed to low oxygen conditions and perfusion flow was modulated to induce preeclamptic characteristics, resulting in reduced barrier function, hormone secretion, and microvilli as well as increased nuclei count. The model was implemented in a titer plate microfluidic platform fully amenable to high-throughput screening. We thus believe this model could aid mechanistic understanding of preeclampsia as well as support future development of effective therapies through target and compound screening campaigns.