An Integrated Organoid-on-a-Chip Platform for Modeling the Human Placental Barrier

Area of Science:

• Biomedical Engineering
• Reproductive Biology
• Toxicology

Background:

• The human placental barrier is crucial for fetal protection and nutrient exchange.
• Existing cell lines and animal models inadequately represent the complex human placental barrier.
• A need exists for advanced models to study placental function and xenobiotic transport.

Purpose of the Study:

• To develop a novel organ-on-a-chip (OOC) model of the human placental barrier.
• To create a biomimetic system that recapitulates key structural and functional features.
• To utilize the model for assessing transbarrier transport and toxicity of compounds.

Main Methods:

• Integration of human JEG-3 trophoblast organoids and human umbilical vein endothelial cells.
• Application of combined fluid shear stress and mechanical strain to promote self-assembly.
• Characterization of the engineered tissue for physiological markers and transport activity.
• Assessment of flavonoid compound permeation across the OOC model.

Main Results:

• Successful self-assembly of a 3D functional placental barrier in the OOC model.
• Demonstrated expression of syncytiotrophoblast markers and secretion of human chorionic gonadotropin.
• Observed enhanced glucose transport activity, indicating functional mimicry.
• Flavonoid permeation was primarily driven by lipophilicity, not molecular size, via passive diffusion.

Conclusions:

• The developed OOC platform provides a biomimetic human placental model.
• This advanced model offers a reliable tool for evaluating placental permeability.
• The platform aids in assessing potential toxicity risks of complex compounds during pregnancy.