Unraveling placental immunity: a 3D model of the human placenta barrier to study trimester-specific inflammatory responses 2536

Abstract Description Placental dysfunction compromises fetal health, leading to serious pregnancy complications like intrauterine growth restriction and preterm birth. Understanding the mechanisms of such dysregulation is critical for improving maternal-fetal health outcomes. To address limitations of existing models, we developed an in vitro 3D bio-printed model of the human placenta barrier(hPB). By incorporating primary trophoblasts, endothelial cells, placental fibroblasts and pericytes, we recapitulated key features of the hPB structure and function during early and late gestational stages. To induce inflammation, we apically exposed both early and late-stage hPBs to 250-500 ng/mL of LPS for 48 hours. LPS treatment revealed term-specific responses. Early-stage trophoblasts exhibited a compensatory response with enhanced nutrient transport and preserved barrier integrity. In contrast, late-stage trophoblasts displayed decreased hormone production, increased inflammation, and impaired barrier function, potentially compromising fetal health. Ongoing computational analysis of the vascular network and incorporation of primary preeclamptic trophoblast will further enhance our understanding of hPB dynamics in healthy and inflammatory conditions. Additionally, our 96-well format allows for high-throughput screening of drugs to assess capacity to modulate LPS effects. Ultimately, by advancing our understanding of hPB function across gestation we aim to improve maternal and fetal health outcomes. Funding Sources NIH NCATS/ FDA Translational Science Interagency Fellowship Topic Categories Mucosal and Regional Immunology (MUC)