Project Objectives
- Develop and validate a perfused co-culture model using primary human placental trophoblasts and umbilical vein endothelial cells.
- Conduct pilot drug testing with caffeine and antipyrine to confirm model functionality.
- Assess clinically relevant drugs used during pregnancy, including metformin and glyburide.
- Evaluate reproducibility and robustness through an inter-laboratory pilot study.
3Rs Impact
- Provides a physiologically relevant human-based model that can replace many preliminary animal studies in reproductive and developmental toxicology.
- Reduces the number of animals required by identifying unsafe compounds before they progress to in vivo testing.
- Enables safer, earlier screening of candidate drugs, reducing follow-up studies in multiple species.
- Improves scientific validity by using human primary cells, ensuring more accurate predictions of fetal exposure.
Background
During pregnancy, medicines taken by the mother may cross the placenta and reach the fetus, potentially causing harm. However, understanding this transfer is challenging: human placental biology is unique, meaning animal models often fail to accurately predict human outcomes. Existing laboratory models rely on immortalised cell lines that do not fully replicate the behaviour of healthy placental tissue, and advanced placenta-on-a-chip systems can absorb some compounds, making drug transfer data unreliable. Ex vivo perfusion of human placentas is considered the gold standard, but is technically demanding, costly, and unsuitable for routine screening.
To address these challenges, this project develops an advanced in vitro co-culture model that brings together the two key cell types forming the materno-fetal barrier: primary trophoblasts (maternal side) and primary human umbilical vein endothelial cells (fetal side). By growing these freshly isolated cells in a controlled perfusion system, the model recreates important physiological features such as cellular polarity, hormone secretion, and flow dynamics. This human-derived platform provides a more realistic, ethical, and scalable way to study materno-fetal drug transfer and offers a promising alternative for early-stage testing in drug development.
