Advancing maternal–fetal research: The promise of placental perfusion models

The human placenta serves as the critical interface between maternal and fetal circulation, orchestrating nutrient transfer, waste elimination, and hormone production throughout pregnancy. Understanding placental function has profound implications for maternal and neonatal health, yet studying this organ in vivo presents significant ethical and methodological challenges. Placental perfusion models have emerged as indispensable tools for advancing our understanding of placental physiology and pathology. The ex vivo dual perfusion model, first developed by Schneider et al., revolutionized placental research by enabling controlled investigation of transplacental transport mechanisms. This technique involves perfusing both maternal and fetal vascular compartments of freshly collected placental cotyledons, maintaining tissue viability for several hours while allowing precise manipulation of perfusion parameters. The model has proven invaluable for studying drug transport kinetics, particularly for medications used during pregnancy, where clinical studies are limited. Recent technological advances have expanded the utility of placental perfusion models. Microfluidic placenta-on-chip devices now replicate the placental barrier at the microscale, incorporating human placental cells and enabling high-throughput screening of pharmaceutical compounds. These platforms offer enhanced reproducibility and reduced tissue requirements compared to traditional perfusion systems. Contemporary applications extend beyond basic transport studies to include investigation of placental responses to hypoxia, infection, and metabolic disorders. Researchers have utilized perfusion models to elucidate mechanisms underlying preeclampsia, intrauterine growth restriction, and gestational diabetes, providing insights into prevention and treatment strategies. Despite their advantages, placental perfusion models have limitations including tissue heterogeneity, limited perfusion duration, and potential artifacts from isolation procedures. Future developments focus on extending tissue viability, incorporating immune cells, and integrating real-time monitoring capabilities. As precision medicine approaches maternal–fetal health, placental perfusion models will remain essential for developing personalized therapeutic strategies and ensuring medication safety during pregnancy.