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First placenta-on-a-chip to help study causes of preterm birth

Tuesday, Jul 26, 2016,15:20 IST By Metrovaartha A A A

Washington | Scientists have developed the first placenta-on-a-chip that can fully model the transport of nutrients across the interface between mother and foetus, an advance that may help identify causes of preterm birth and ways to prevent it.

The flash-drive-sized device contains two layers of human cells and microfluidic channels on either side of those layers, that allows researchers to study how molecules are transported through, or are blocked by, that interface.

The placenta-on-a-chip developed by the University of Pennsylvania provides a unique capability to mimic and study the function of that human organ in ways that have not been possible using traditional tools. Prematurely born babies experience lifelong, debilitating consequences, but the underlying mechanisms of this condition are not well understood due in part to the difficulties of experimenting with intact, living human placentae.

The researchers’ placenta-on-a-chip is a clear silicone device with 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, are grown. On the other side are endothelial cells, found on the interior of foetal blood vessels.

The layers of those two cell types mimic the placental barrier, the gatekeeper between the maternal and foetal circulatory systems. That barrier mediates all transport between mother and foetus during pregnancy. Nutrients, but also foreign agents like viruses, need to be either transported by that barrier or stopped, said Cassidy Blundell, graduate student at University of Pennsylvania.

One of the most important function of the placental barrier is transport, so it’s essential for us to mimic that functionality, said Dan Huh, Assistant Professor at University of Pennsylvania, who led the research. The researchers demonstrated that the two layers of cells continue to grow and develop while inside the chip, undergoing a process known as syncytialisation.

During pregnancy, the placental trophoblast cells actually fuse with one another to form an interesting tissue called syncytium, Huh said. The barrier also becomes thinner as the pregnancy progresses, and with our new model we’re able to reproduce this change, he said. The team validated the new model by showing glucose transfer rates across this syncytialised barrier matched those measured in perfusion studies of donated human placentae.

While useful in providing this type of baseline, donated placental tissue can be problematic for doing many of the types of studies necessary for fully understanding the structure and function of the placenta, especially as it pertains to diseases and disorders.