Characterization and Tracking of Immune Cell Dynamics on a Placenta-on-a-Chip Platform

Abstract

Early gestation placental immunology and nutrient transport have been poorly understood due to limitations in ethical constraints and inadequate animal model replication. Current placenta-on-a-chip models offer a controlled approach for placental studies but lack precision in early gestation stages. Before developing a fully 3D printed microfluidic chip that models early placental interactions between placental and immune cells, we are characterizing 3D-cultured JAR human trophoblast cells and innate immune THP-1 human monocyte cells in a degradable synthetic PEG-RGD-VPM hydrogel. The 3D culturing approach allows us to examine cell behavior in a physiologically relevant context, enhancing our understanding of early placental conditions. Experimentation began with confirming cell viability and metabolic activity within the synthetic hydrogel through an Alamar Blue assay and live/dead cell staining. Upon discovering viability, cell migration of THP-1 cells suspended in media into JAR-encapsulated hydrogels was examined relative to a control blank hydrogel across 5 days of incubation through confocal microscopy. Results suggested JAR cells have some modulation in THP-1 migration behavior, as notable differences in cell counts between the two groups were observed on day 5. Lastly, an ELISA examining the pro-inflammatory cytokine TNF-𝛼 between co-cultured JAR cells and M0 macrophage cells (differentiated THP-1s) suggested JAR cells sustaining an inflammatory environment with the M0 cells after 3 days of incubation relative to a control blank hydrogel containing M0 cells. The results of this project confirmed cellular communication and immune interactions between placental trophoblast cells and innate immune cells.

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