Amnion-on-a-chip: modeling human amniotic development in mid-gestation from pluripotent stem cells

Amnion serves to create a protective environment for growing fetus and the study of amniotic development will greatly facilitate our understanding of normal and diseased pregnancy. However, it remains poorly known due to the lack of ideal human models. Herein, we present an integrative strategy to generate amnion-like cavity tissue from human pluripotent stem cells (hPSCs) in a amnion-on-a-chip device by combining bioengineering approach and developmental biology principle. hPSCs could self-organize into amnion epithelial cavity in a perfusable 3D culture microchip, resembling human amniotic development in mid-gestation. These cavities exhibited the critical features of amnion tissue in terms of morphological characteristics, markers expression and transcriptome analysis. RNA-seq revealed a set of amnion-specific genes were highly expressed in obtained cavities, suggesting the amnion epithelium derived from hPSC. Moreover, the amnion specific marker of KRT24 in mid-gestation was highly expressed at mRNA and protein level, verifying the high maturation of amnion tissues after long-term 3D culture and differentiation for up to 20 days. These new findings demonstrate the potentials of this new aminion-on-a-chip model to investigate the essential biological events in human amnion in normal and disease states by integrating microengineering technology with stem cell biology.