Trophoblast organoids with physiological polarity model placental structure and function

Area of Science:

• Reproductive Biology
• Developmental Biology
• Cell Biology

Background:

• Human trophoblast organoids (TOs) are valuable 3D ex vivo models for studying placental development, physiology, and pathology.
• Previous work demonstrated TOs' utility in modeling trophoblast innate immune signaling and viral infections.

Approach:

• Developed a novel method to culture TOs that recapitulates the in vivo cellular orientation of chorionic villi.
• Cultured standard TOs (STB inside) in suspension with gentle agitation to promote development into STB-out organoids (STB on outer surface).
• Utilized membrane capacitance measurements to characterize syncytia size on the organoid surface.

Key Points:

• STB-out organoids exhibit an in vivo-like cellular orientation with syncytiotrophoblast (STB) on the outer surface and cytotrophoblasts (CTBs) internally.
• STB-out organoids secrete significantly higher levels of key STB-associated hormones and cytokines, including hCG and IFN-λ2.
• STB-out organoids possess large syncytia (>50 nuclei) on their surface, contrasting with smaller syncytia (<10 nuclei) and mononuclear cells in STB-in organoids.

Conclusions:

• This culture method enables the study of placental biology under more physiologically relevant conditions.
• The STB-out organoid model provides a powerful tool for investigating trophoblast function and placental pathologies.
• Further research into placental development and disease can benefit from this advanced ex vivo model.