Modeling Preeclampsia: From 2D Cultures to Placenta-on-a-Chip Technologies

Preeclampsia is a complex pregnancy disorder marked by hypertension and proteinuria, often resulting in significant maternal and fetal morbidity and mortality. Understanding its pathogenesis is crucial for developing effective diagnostic and therapeutic strategies. Given the placenta’s central role in preeclampsia, it remains a focal point for research. This review offers a comprehensive overview of current preeclampsia modeling studies. It starts with an introduction to preeclampsia, emphasizing its impact on maternal and fetal health. The review then discusses placental development and structure, including comparisons between human and animal model placentas, to establish a foundation for understanding placental involvement in preeclampsia. The pathogenesis of preeclampsia is explored, highlighting key molecular and cellular mechanisms. Various cell models, including 2D and 3D static cultures and placenta-on-a-chip models, are reviewed to elucidate their contributions to studying preeclampsia pathophysiology and their potential applications in drug discovery and personalized medicine. This review aims to consolidate existing knowledge and stimulate further research into the etiology and management of preeclampsia. © 2025 Elsevier B.V., All rights reserved.