The placenta is oddly ephemeral for an organ. It appears, grows, and changes throughout the course of pregnancy, and then is gone. After delivery, researchers have a few hours at most to work with donated placentae before the tissue dies, and that is the best among limited options. Experimenting on the organ in vivo is effectively impossible.
These limitations mean that the placenta remains relatively mysterious as well. Standing as a gatekeeper to the developing fetus, it lets in nutrients and blocks harmful foreign invaders, but identifying exactly how diseases and disorders impact this role requires more study.
With that challenge in mind, researchers in the School of Engineering and Applied Science and the Perelman School of Medicine have developed a new “placenta-on-a-chip.” The flash-drive-sized device is the first of its kind that that can fully model the transport of nutrients across the placental barrier, making it an important new avenue for research on this poorly understood organ.
The research was led by Dan Huh, the Wilf Family Term Assistant Professor of Bioengineering in Penn Engineering, and Cassidy Blundell, a graduate student in the Huh lab. They collaborated with Samuel Parry, the Franklin Payne Professor of Obstetrics and Gynecology, and other Penn Medicine researchers.
Like other organs-on-chips developed by Huh, such as ones that simulate lungs, intestines, and eyes, the placenta-on-a-chip provides a unique capability to conduct studies on human tissue that aren’t possible using conventional techniques. It contains two layers of human cells that model the interface between mother and fetus. Microfluidic channels on either side of those layers allow researchers to study how molecules are transported through, or are blocked by, that interface.
In 2013, Huh and colleagues at Seoul National University conducted a preliminary study to create a microfluidic device for culturing the two types of cells. The Penn researchers have now 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 says. “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,” he says.
Research on the team’s placenta-on-a-chip is part of a nationwide 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. A $10 million grant from the organization established the Prematurity Research Center at Penn—one of five such centers nationwide—and enabled the collaboration between Penn Medicine and Penn Engineering.
Encouraged by their results, the Penn researchers aim to expand.
“We’ve reached out to the principal investigators at the other four March of Dimes sites and offered to provide them this model to use in their experiments,” Parry says.