Healthy and diseased placental barrier on-a-chip models suitable for standardized studies

• DOI: 10.1016/j.actbio.2023.04.033
• Publication Date: 2023-04-27T01:16:32Z
• Authors: Gwenaëlle Rabussier; Ivan Bünter; Josse Bouwhuis; Camilla Soragni; Torben van Zijp; Chee Ping Ng; Karel Domansky; Leon J. de Windt; Paul Vulto; Colin E. Murdoch; Kristin M. Bircsak; Henriëtte L. Lanz
• Keywords: Hypoxia; Barrier function

Pathologies associated with uteroplacental hypoxia, such as preeclampsia are among the leading causes of maternal and perinatal morbidity in world. Its fundamental mechanisms yet poorly understood due to a lack good experimental models. Here we report an vitro model placental barrier, based on co-culture trophoblasts endothelial cells against collagen extracellular matrix microfluidic platform. The yields functional syncytium barrier properties, polarization, secretion relevant membrane components, thinning materno-fetal space, hormone secretion, transporter function. is exposed low oxygen conditions perfusion flow modulated induce pathological environment. This results reduced function, microvilli well increased nuclei count, characteristics preeclamptic placentas. implemented titer plate-based platform fully amenable high-throughput screening. We thus believe this could aid mechanistic understanding other pathologies hypoxia/ischemia, support future development effective therapies through target compound screening campaigns. STATEMENT OF SIGNIFICANCE: human placenta unique organ sustaining fetal growth but also source severe pathologies, preeclampsia. Though cause mortality world, remains untreatable To better understand pathology, have developed 3D models device. allows parallel culture 40 perfused physiological miniaturized barriers, comprising differentiated endothelium that been validated for functions. Exposure hypoxic ischemic environment enabled mimicking high-throughput, which lead pathology development.