Placental Barrier-on-a-Chip: Modeling Placental Inflammatory Responses to Bacterial Infection.

Abstract

Placental inflammation, as a recognized cause of preterm birth and neonatal mortality, displays extensive placental involvement or damage with the presence of organisms. The inflammatory processes are complicated and tightly associated with increased inflammatory cytokine levels and innate immune activation. However, the deep study of the underlying mechanisms was limited by conventional cell and animal models because of great variations in the architecture and function of placenta. Here, we established a microengineered model of human placental barrier on the chip and investigated the associated inflammatory responses to bacterial infection. The multilayered design of the microdevice mimicked the microscopic structure in the fetal-maternal interfaces of human placenta, and the flow resembled the dynamic environment in the mother's body. Escherichia coli (E. coli), one of the predominant organisms found in fetal organs, were applied to the maternal side, modeling acute placental inflammation. The data demonstrated the complex responses including the increased secretion of inflammatory cytokines by trophoblasts and the adhesion of maternal macrophages following bacterial infection. Particularly, transplacental communication was observed between two placental cells, and implied the potential role of trophoblast in fetal inflammatory response syndrome in clinic. These complex responses are of potential significance to placental dysfunctions, even abnormal fetal development and preterm birth. Collectively, placental barrier-on-a-chip microdevice presents a simple platform to explore the complicated inflammatory responses in human placenta, and might help our understanding of the mechanisms underlying reproductive diseases.