DETERMINING THE EFFECT OF EXTRACELLULAR MICROENVIRONMENT ON TROPHOBLAST INVASION USING A BIOPRINTED PLACENTA MODEL
Fisher, John P
Kim, Peter CW
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Preeclampsia is a leading cause of maternal and perinatal morbidity and mortality, affecting 8% of all pregnancies. Currently, the only effective treatment for preeclampsia is the premature delivery of the fetus and placenta resulting in significant fetal morbidity. In early pregnancy, fetal trophoblast cells invade and remodel maternal spiral arteries in the uterine wall to create the high capacitance organ of placenta. The uterine spiral arteries in preeclampsia, however, remain narrow and poorly remodeled. The exact mechanisms of how trophoblast invade and remodel the spiral arteriole are not known, and there is a paucity of relevant experimental models to study the mechanisms in human pregnancy. The goal of this work was to develop a dynamic bioprinted placenta model and use it to determine the role of extracellular microenvironment in preeclampsia. We began by developing a 3D placenta model that could quantify trophoblast invasion rates through bioprinting. Then we used decellularization techniques to isolate and established the necessary role of placental basement membrane protein to achieve effective trophoblast invasion. Finally, we used the dynamic bioprinted placenta model and found trophoblast impairs the flow-induced angiogenesis of endothelial cells, a process that plays a central role in preeclampsia. Overall, we described the significant impact of the extracellular microenvironment on the behavior trophoblast and/or endothelial cells, an area that is less investigated but appeared to be critical in the pathogenesis of preeclampsia. Moreover, the approach presented in this work can be used to screen and develop novel therapeutics and biomarkers not only for preeclampsia but also other diseases such as cancer metastasis and wound healing.