Researchers at the University of Pennsylvania’s School of Engineering and Applied Science have demonstrated the feasibility of their “organ-on-a-chip” platform in studying how drugs are transported across the human placental barrier.
Some maternally-administered medications can enter the fetal bloodstream, but how the placenta determines which molecules can get through is still poorly understood. The ways of testing this process are limited. Animal models don’t capture important details of human physiology, most in vivo research can’t be ethically performed and placentas donated after birth are only viable for a few hours, making it difficult to properly conduct complicated transport experiments.
A small number of drugs have been tested via this “ex vivo placental perfusion” method, however. By comparing the results of transport experiments conducted on their placenta-on-a-chip, the Penn team demonstrated their benchtop system could be an effective stand-in for a living organ in such research.
The study was led by Dan Huh, Wilf Family Term Assistant Professor in Bioengineering in Penn’s School of Engineering and Applied Science, and Cassidy Blundell, a graduate student in the Huh lab. Other lab members, Yoon-Suk Yi, Lin Ma, Emily Tess, Megan Farrell and Andrei Georgescu, contributed to the study. They collaborated with Lauren M. Aleksunes, an associate professor in Rutgers University’s Ernest Mario School of Pharmacy.
The Penn team’s placenta-on-a-chip is a small block of silicone that houses 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, which determines what passes from the maternal to the fetal circulatory systems.
The placenta-on-a-chip aims to replicate the complicated, intertwined structures in the placental barrier. Their latest study was featured on the cover of Advanced Healthcare Materials.
Further research and validation studies will be necessary before the placenta-on-a-chip sufficiently replicates its in vivo counterpart for the purposes of clinical testing.
Beyond pharmaceuticals, the Penn team’s placenta-on-a-chip would be useful for better understanding the health impacts of a variety of things that could potentially cross into the fetal bloodstream.