The first placenta-on-a-chip can fully model the transport of nutrients between mother and fetus.
The flash-drive-sized device contains two layers of human cells that model the interface. Microfluidic channels on either side of those layers allow researchers to study how molecules are transported through, or are blocked by, that interface.
Like other organs-on-chips—such as ones developed to simulate lungs, intestines, and eyes—the 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.
Research on the team’s placenta-on-a-chip is part of a US effort sponsored by the March of Dimes to identify causes of preterm birth and ways to prevent it. Prematurely born babies may experience lifelong, debilitating consequences, but the underlying mechanisms of this condition are not well understood due in part to the difficulties of experimenting with intact, living human placentas.
How it works
The clear silicone device has 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.
The layers of those two cell types mimic the placental barrier, the gatekeeper between the maternal and fetal circulatory systems.
The study was published in the journal Lab on a Chip.
“That barrier mediates all transport between mother and fetus during pregnancy,” says Cassidy Blundell, a graduate student at the University of Pennsylvania who co-led the study. “Nutrients, but also foreign agents like viruses, need to be either transported by that barrier or stopped.”
“One of the most important function of the placental barrier is transport,” says study co-leader Dan Huh, an assistant professor of bioengineering in Penn’s School of Engineering and Applied Science, “so it’s essential for us to mimic that functionality.”
More accurate simulation
In 2013, Huh and his collaborators at Seoul National University conducted a preliminary study to create 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.
In their new study, the Penn researchers have demonstrated that the two layers of cells continue to grow and develop while inside the chip, undergoing a process known as “syncytialization.”
“The placental cells change over the course of pregnancy,” Huh explains. “During pregnancy, the placental trophoblast cells actually fuse with one another to form an interesting tissue called syncytium. The barrier also becomes thinner as the pregnancy progresses, and with our new model we’re able to reproduce this change.
“This process is very important because it affects placental transport and was a critical aspect not represented in our previous model.”
‘Least understood organ in the human body’
The team validated the new model by showing glucose transfer rates across this syncytialized barrier matched those measured in perfusion studies of donated human placentas.
While useful in providing this type of baseline, donated placental tissue can be problematic for doing many of the types of studies necessary for fully understanding the structure and function of the placenta, especially as it pertains to diseases and disorders.
“The placenta is arguably the least understood organ in the human body,” Huh says, “and much remains to be learned about how transport between mother and fetus works at the tissue, cellular, and molecular levels. An isolated whole organ is an not ideal platform for these types of mechanistic studies.”
“Beyond the scarcity of samples,” Blundell says, “there’s a limited lifespan of how long the tissue remains viable, for only a few hours after delivery, and the system that is used to perfuse the tissue and perform transport studies is complex.”
While the placenta-on-a-chip is still in the early stages of testing, researchers at Penn and beyond are already planning to use it in studies on preterm birth.
The March of Dimes and an award from the National Institutes of Health supported the project.
Source: University of Pennsylvania