Prematurely born babies may experience lifelong, debilitating consequences with the underlying mechanisms of this condition not well understood, due in part to the difficulties of experimenting with intact, living human placenta. Now, researchers at the University of Pennsylvania have developed the first ever placenta-on-a-chip that can fully model the transport of nutrients across the placental barrier. The team state that like other organs-on-chips, such as ones developed to simulate lungs, intestines and eyes, their placenta-on-a-chip provides a unique capability to mimic and study the function of that human organ in ways that have not been possible using traditional tools. The study is published in the journal Lab on a Chip.
Previous studies show that much remains to be learned about how placental transport between mother and fetus works at the tissue, cellular and molecular levels. An isolated whole organ is not an ideal platform for these types of mechanistic studies. This is due to the fact that beyond the scarcity of samples there’s a limited lifespan of how long the tissue remains viable for only a few hours after delivery, and the system is too complex. Earlier studies from the lab developed a microfluidic device for culturing trophoblast cells and fetal endothelial cells. This model, however, lacked the ability to form physiological placental tissue and accurately simulate transport function of the placental barrier. The current study demonstrates that the two layers of cells continue to grow and develop while inside the chip, undergoing a process known as ‘syncytialization’, where the placental trophoblast cells fuse with one another to form a natural barrier.
The current study developed a placenta-on-a-chip using a clear silicone device with two parallel microfluidic channels separated by a porous membrane. On one side of those pores, trophoblast cells, which are found at the placental interface with maternal blood, are grown. On the other side are endothelial cells, found on the interior of fetal blood vessels. Results show that the layers of the two cell types mimic the placental barrier, the gatekeeper between the maternal and fetal circulatory systems.
The group explain that this barrier mediates all transport between mother and fetus during pregnancy, with nutrients and foreign agents like viruses, needing to be either transported by that barrier or stopped; therefore, it’s essential to mimic that functionality. Results show that glucose transfer rates across this syncytialized barrier matched those measured in perfusion studies of donated human placenta.
The team surmise that with their new model they were able to reproduce syncytium and the barrier thinning during pregnancy progresses. For the future, the researchers state that while the placenta-on-a-chip is still in the early stages of testing, they are already planning to use it in studies on preterm birth. They conclude that eventually, they hope to leverage the unique capabilities of their model to demonstrate the potential of organ-on-a-chip technology as a new strategy to innovate basic and translational research in reproductive biology and medicine.
Source: University of Pennsylvania