Placenta-On-Chip Studies Drug Transport Into Fetal Bloodstream
Tony Pallone | February 18, 2018More news from the growing field of organ-on-chip technology: Researchers at the University of Pennsylvania's School of Engineering and Applied Science, also known as Penn Engineering, have used a placenta-on-chip platform to study how drugs are transported across the human placental barrier.
Organ-on-chip technology is medicine’s newest way to study conditions and dynamics that would be unethical, or even impossible, to study on living subjects. It may also lead the way to personalized drug therapies. Recently we’ve told you about chips that model heart disease, study the intestinal effects of radiation exposure and tested liver reaction to hepatitis B infection. These are just a few examples of the technology, which is based on microfluidics — a multidisciplinary field dealing with fluids geometrically constrained to the sub-millimeter scale.
For the Penn scientists, the goal is to understand how the placenta determines which molecules get through to the fetal bloodstream, which is important for controlling maternally administered medications. The importance was illustrated tragically in the 1960s, when thalidomide, a drug marketed as safe for pregnant women in the treatment of morning sickness, found its way across the placental barrier and led to tens of thousands of birth defects and deaths.
Most placental transport experiments today are done with placentas donated after birth — but these are only viable for a few hours. The Penn team has demonstrated that their benchtop system can be an effective stand-in for a living organ, with a much longer lifespan.
The device is a small block of silicone housing two microfluidic channels separated by a porous membrane. The researchers grow human trophoblast cells on one side of the membrane and endothelial cells on the other: The layers of those two cell types mimic the placental barrier. By adding different molecules to the blood-like fluid flowing through the "maternal" microfluidic channel, the researchers can measure the rate at which they transfer to the "fetal" channel and how much they accumulate in the barrier itself.
"This study has given us confidence that the placenta-on-a-chip has tremendous potential as a screening platform to assess and predict drug transport in the human placenta," said Dan Huh, an assistant professor in bioengineering in Penn's School of Engineering and Applied Science.
Beyond pharmaceuticals, the Penn team's placenta-on-chip could be useful for better understanding the health impacts of other substances that could cross into the fetal bloodstream. "We'd like to use this system to test things beyond drugs, such as herbal supplements, vitamins, and a whole host of things that women might take over the course of pregnancy," added Cassidy Blundell, a graduate student in the Huh lab.
The study appears in a recent edition of the journal Advanced Healthcare Materials.