In a recent study, researchers at Penn's School of Engineering and Applied Science have made significant progress in understanding how drugs are transferred across the human placental barrier.
According to a summary of the study in Drug Target Review, the Penn researchers successfully demonstrated their technique of “placenta-on-a-chip,” which can act as an "effective stand-in for a living organ in such research."
Several drugs had previously been tested through complicated transplant experiments involving donated placentas, in an attempt to further researcher’s understanding of exactly how the placenta determines which molecules to allow through.
Still, these tests are rather unreliable, as placentas that are donated are only viable for a handful of hours following birth. Ultimately, as Drug Target Review reported, by comparing the results of such experiments with their own conducted with the placenta-on-a-chip system, the Penn team demonstrated that this system could be an effective replacement for donated placentas in related research.
With the placenta-on-a-chip, researchers aimed to model the transport of nutritional molecules through the placental barrier, using two growing layers of human cells.
According to Drug Target Review, “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 foetal circulatory systems.”
As Blundell further told Philly Voice, "That [placental] barrier mediates all transport between mother and fetus during pregnancy. Nutrients, but also foreign agents like viruses, need to be either transported by that barrier or stopped.”
Testing of this kind on human placental behavior has major implications for further research. As Technology Network reported, pregnant women have been historically barred from participating in clinical drug trials.
This can have negative consequences, as demonstrated by the case of thalidomide, a morning sickness drug with the capability to transport across the human placental barrier that recently was directly linked to tens of thousands of birth defects and deaths.
In the future, Penn researchers are hopeful their new “organ-on-a-chip” system will be able to prevent the manufacturing and commercialization of drugs that lead to developmental issues.
As Huh told Philly Voice, "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 not an ideal platform for these types of mechanistic studies.”
Further research was also provided by lab members Yoon-Suk Yi, Lin Ma, Emily Tess, Megan Farrell and Andrei Georgescu. They also collaborated with Lauren M. Aleksunes, an associate professor in Rutgers University’s Ernest Mario School of Pharmacy.