Organ-on-a-Chip Device Mimics Structure and Function of Human Placental Barrier

A novel lab-on-a-chip device mimics the structure and function of the human placental barrier and allows researchers to carry out in vitro studies on factors influencing fetal development.

During human pregnancy, the fetal circulation is separated from maternal blood in the placenta by two cell layers – the fetal capillary endothelium and placental trophoblast. This placental barrier plays an essential role in fetal development and health by tightly regulating the exchange of endogenous and exogenous materials between the mother and the fetus.

To mimic the characteristic architecture of the human placental barrier, investigators at the University of Pennsylvania (Philadelphia, USA) created on a silicon chip a multilayered microfluidic system that enabled co-culture of human trophoblast cells and human fetal endothelial cells in a physiologically relevant spatial arrangement. The device comprised 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, were grown. On the other side were endothelial cells, found on the interior of fetal blood vessels.

The co-culture model was designed to induce progressive fusion of trophoblast cells and to form a syncytialized epithelium that resembled the in vivo syncytiotrophoblast. The system also allowed the cultured trophoblasts to form dense microvilli under dynamic flow conditions and to reconstitute expression and physiological localization of membrane transport proteins, such as glucose transporters (GLUTs), critical to the barrier function of the placenta.

In a proof-of-principle study, the investigators used the "placenta-on-a-chip" device to demonstrate physiological transport of glucose across the artificial maternal-fetal interface. They reported in the May 20, 2016, online edition of the journal Lab on a Chip that the rate of maternal-to-fetal glucose transfer in this system closely approximated that measured in ex vivo perfused human placentas.

"The placenta is arguably the least understood organ in the human body," said senior author Dr. Dongeun Huh, professor of bioengineering at the University of Pennsylvania, "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 not an ideal platform for these types of mechanistic studies. "

"The placental cells change over the course of pregnancy," said Dr. Huh. "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 are able to reproduce this change. Eventually, we hope to leverage the unique capabilities of our model to demonstrate the potential of organ-on-a-chip technology as a new strategy to innovate basic and translational research in reproductive biology and medicine."

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