Recapitulating gestational progression: a high-throughput 3D bioprinted vascularized human placenta demonstrating stage-specific molecular and functional signatures of human pregnancy

Abstract

Abstract The placenta is a highly dynamic organ that supports the growth and development of the fetus during gestation. Malfunction of the placenta causes disorders of the pregnancy, including preeclampsia and pre-term birth. The study of the pathophysiology of the placenta throughout pregnancy has been hindered by limited access to the human placenta and lack of predictive cellular and animal models. Here, we describe 3D bioprinted human placenta barrier (hPB) tissue models using primary human trophoblasts and stroma cells that recapitulate the physiology of the human placenta at early and late stages of gestation. These bioprinted vascularized hPB tissue models mimic the architecture and function early and late-stages human placenta, including barrier function, nutrient uptake, transporters activity and hormones secretion. Assembled in a 96-well transwell plate format, this deeply characterized platform provides a robust high-fidelity system for predictive screening of therapeutics and potentially hazardous agents for placenta diseases and safety, and a better understanding of placental pathophysiology.