Biomimetic Placenta-Fetus Model Demonstrating Maternal–Fetal Transmission and Fetal Neural Toxicity of Zika Virus

Recent global epidemics of viral infection such as Zika virus (ZIKV) and associated birth defects from maternal–fetal viral transmission highlights the critical unmet need for experimental models that adequately recapitulates the biology of the human maternal–fetal interface and downstream fetal development. Herein, we report an in vitro biomimetic placenta-fetus model of the maternal–fetal interface and downstream fetal cells. Using a tissue engineering approach, we built a 3D model incorporating placental trophoblast and endothelial cells into an extracellular matrix environment and validated formation of the maternal–fetal interface. We utilized this model to study ZIKV exposure to the placenta and neural progenitor cells. Our results indicated ZIKV infects both trophoblast and endothelial cells, leading to a higher viral load exposed to fetal cells downstream of the barrier. Viral inhibition by chloroquine reduced the amount of virus both in the placenta and transmitted to fetal cells. A sustained downstream neural cell viability in contrast to significantly reduced viability in an acellular model indicates that the placenta sequesters ZIKV consistent with clinical observations. These findings suggest that the placenta can modulate ZIKV exposure-induced fetal damage. Moreover, such tissue models can enable rigorous assessment of potential therapeutics for maternal–fetal medicine.