Scientists at the Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National Health System , in partnership with the University of Maryland, are the first to create a 3D bioprinted placenta model and use it to study preeclampsia, a life-threatening pregnancy complication.
Bioprinting is the three-dimensional printing of biological tissue and organs through the layering of living cells, with cell function and viability preserved within the printed structure. Because the institute’s bioprinted placenta model mimics the organ’s complex cellular structure, the model creates unprecedented opportunities to understand and develop new treatments for life-threatening maternal conditions involving the placenta. The study of the 3D bioprinted model is published in American Chemical Society (ACS) Biomaterials Science & Engineering.
Preeclampsia is the leading cause of maternal and perinatal morbidity and mortality, affecting three to eight percent of all pregnancies. The cause of preeclampsia is uncertain and the only treatment is premature delivery.
In their published report, the scientists used the bioprinted model to observe the migration of special cells in the placenta called trophoblasts, which attach to the uterine wall and then proceed to invade the tissues of the uterus during the first stage of pregnancy. These trophoblasts eventually reach deep into the wall and connect with the mother’s blood vessels, which is a vital stage in the establishment of pregnancy as the placenta takes on its role of nourishing the fetus. Some theories about the cause of preeclampsia suggest that the trophoblasts do not migrate normally. In order to study this, the research team first needed to create a bioprinted placenta model containing the key cellular, biochemical, and extra cellular matrix components to recreate the interaction for trophoblast migration.
“Our study provides a proof of concept that a 3D bioprinted placenta model is a viable way to study and understand the dynamics of cell migration in the formation of the placenta, said John P. Fisher, chair of the Fischell Department of Bioengineering, University of Maryland. “What we have learned from this initial study is a significant step toward understanding the cause of preeclampsia and a potential therapy.”
The scientists used the 3D placenta model to evaluate the effect of epidermal growth factor (EGF), on the migratory behavior of trophoblasts. Epidermal growth factor stimulates cell growth, proliferation, and differentiation. From the study, the team learned that EGF has a positive affect on the migration of trophoblasts, suggesting that EGF may have value as a potential therapeutic agent for preeclampsia.
One of the reasons the scientists could learn more about the dynamic behavior of the trophoblast cells is because of the 3D quality of the bioprinted model.
“A 3D model provides you with a much clearer picture of cell behavior,” said Che-Ying Kuo, study author and researcher with Fischell Department of Bioengineering at University of Maryland and Sheikh Zayed Institute. “A 2D placenta model, which had been used in previous studies, will only show you that the cells have moved, while a 3D model will show you how they move, where they move, and if they move together or separately.”
The researchers say this model is the first step toward building a more sophisticated bioengineered placenta model as a powerful tool to test and develop novel treatments for preeclampsia. It also offers scientists a new avenue for study of a wider variety of placenta-related maternal complications including placenta accreta and placenta previa.
“Until now, there has been a lack of effective experimental placenta models,” said Dr. Peter C. Kim, vice president and associate surgeon in chief, Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National Health System. “Animal models are not directly relevant and are misleading as the placentation process in humans is very different from those of other species. At the same time, clinical testing involving pregnant mothers is not feasible due to ethical and regulatory considerations, so a new solution was needed.”
These factors, Dr. Kim added, contributed to the decision at Children’s National to focus on creating a 3D bioprinted placenta model, because the innovation could yield valuable information that could save the lives of mothers and babies.
Article: Development of a 3D Printed, Bioengineered Placenta Model to Evaluate the Role of Trophoblast Migration in Preeclampsia, Che-Ying Kuo, Avinash Eranki, Jesse K. Placone, Kelly R. Rhodes, Helim Aranda-Espinoza, Rohan Fernandes, John P. Fisher, and Peter C. W. Kim, American Chemical Society (ACS) Biomaterials Science & Engineering, doi: 10.1021/acsbiomaterials.6b00031, published online 30 April 2016.