3-D cell placenta model mimics development, microbial resistance

Three beads covered in placental cells (labelled green). Nuclei are blue and cell junctions are red. Coyne lab, University of Pittsburgh

Each of us enters the world attached to our mother by a placenta. This organ develops in a woman’s uterus (womb) during pregnancy. Anchored to the uterus wall, it connects to the developing fetus through the umbilical cord.

The placenta acts as a complex support system for the fetus. It links the mother’s and developing babies’ blood supplies. It carries oxygen and nutrients from the mother’s blood to the fetus, and removes carbon dioxide and other waste. It also makes hormones that help the fetus grow and develop.

The placenta serves as a barrier as well, blocking the transfer of toxins, bacteria, and viruses from the mother. However, some viruses—as well as alcohol, nicotine and other drugs—can cross the placenta from the mother, potentially harming the unborn baby.

Much of the placenta is composed of cells called trophoblasts. A form of these cells fuse together to create a specialized layer of cells that aid in the exchange of gases and nutrients. These cells, called syncytiotrophoblasts, are directly bathed in maternal blood beginning in the later stages of the first trimester of pregnancy. They form a key cellular barrier between the maternal and fetal compartments. Studying these cells and their functions has been difficult.

A team led by Dr. Carolyn Coyne at the University of Pittsburgh Schools of the Health Sciences set out to develop a cell culture model to better understand how these cells fuse, develop, and subsequently protect against microbial infections. The research was funded in part by NIH’s National Institute of Allergy and Infectious Diseases (NIAID) and Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). Details of the work appeared on March 4, 2016, in Science Advances.

A bead covered with trophoblasts that have fused to form cells with multiple nuclei (blue). Cell junctions are labelled red.Coyne lab, University of Pittsburgh

The scientists studied human JEG-3 trophoblast cells. These cells are derived from a tumor that originated from placental trophoblasts. They are a commonly used cell line model of the placenta. The team grew the cells on beads in a bioreactor, a rotating wall vessel initially designed by NASA. This 3-D system exposes cells to shear and rotational forces that more closely mimic the placental environment than a 2-D culture dish can.

When the cells grew in the bioreactor along with another cell type that helps make up blood vessels, they took on more characteristics of mature syncytiotrophoblasts than cells grown in 2-D culture. The cells fused and secreted placental hormones. They also expressed many genes in a pattern similar to that seen in cells derived from full-term human placentas.

The researchers infected the cells with several strains of fluorescently-tagged parasites. The 3-D cultured cells were resistant to infection by viruses and Toxoplasma gondii, the parasite that causes toxoplasmosis—a disease that can cause harm to the fetus. 

“With this model, we can experiment with different biological factors to see what might allow an infectious agent to get through the placental barrier to the fetus,” says co-investigator Dr. Jon P. Boyle.

The researchers plan to use the model to better understand how pathogens such as Zika and those that cause the group of infections known as “TORCH” (toxoplasmosis, rubella, cytomegalovirus, herpes simplex, and HIV) cross the placental barrier.

—by Carol Torgan, Ph.D.