(53h) Investigating Molecular Interactions of the Placenta for Prenatal Treatment and Testing

The placenta is essential for healthy pregnancy, controlling nutrient and waste transport, but it remains the least understood human organ. Placental trophoblast cells have great potential to provide information about pregnancy complications both fundamentally and clinically during pregnancy. Here we have used both biomaterial and diagnostic techniques in order to develop methods to better understand this maternal-fetal interface and enhance non-invasive prenatal testing.

In order to understand how small molecule and environmental toxins may interact with the maternal-fetal interface, we have developed a placental lipid bilayer mimic. We extracted lipids from primary trophoblast cells, 1^st trimester representative HTR-8 trophoblast cells, and 3^rd trimester representative TCL-1 trophoblast cells. From the primary lipid compositions, we observe significant differences between primary, HTR-8, and TCL-1 trophoblasts. We have used this composition to develop synthetic placental lipid vesicles. Using quartz crystal microbalance with dissipation we developed lipid bilayers containing the placental lipid composition for future interaction studies. This work aims to provide an effective tool for rapid understanding of how molecules interact with the maternal-fetal interface, potentially impacting prenatal and future maternal health.

In addition to having a better understanding of placenta-molecular interactions, improved non-invasive diagnostics can also greatly improve future maternal and child health. Most current prenatal diagnostics are invasive procedures with risk of miscarriage and infection. Obtaining a whole fetal trophoblast cell would provide the entire fetal genome and can be sampled non-invasively through a cervical swab. However, this sample contains a heterogeneous population of cervical cells, mucus, and a small quantity of trophoblast cells. We have developed a label-free method to enrich trophoblast cells from the clinical cervical samples using differential cell settling in solution and inclined plane cell flow. Our methods have provided a 700% purity increase of trophoblast cells within the sample. We have then integrated our enriched trophoblast population into an automated cell picking platform. Here, we successfully isolated trophoblast cells free of maternal debris.

Ultimately, this work provides new methods to understand and use trophoblast cells for the improvement of maternal and fetal health. By improving this understanding, risk to a developing fetus can be minimized, treatment plans can be better informed, and new therapies can be screened.