Category: Micro- and Nanotechnologies
The placenta is a highly specialized organ that is essential to the progression of a successful pregnancy. However, despite its critical importance, it is considered one of the least understood organs in the human body. During pregnancy, the fetal and maternal circulations are separated by a thin multilayered structure known as the placental barrier. This interface plays a critical role in fetal development by tightly regulating the exchange of endogenous and exogenous materials between the mother and fetus. Late in gestation, it consists of two cell layers - the syncytiotrophoblast and fetal endothelium. We present here the placenta-on-a-chip, a microengineered in vitro system that recapitulates the structural and functional complexity of the placental barrier. Our model is a multilayered microfluidic device that enables co-culture of human trophoblast cells and human fetal endothelial cells in a physiologically relevant spatial arrangement that mimics the structure of the in vivo placental barrier. Trophoblast cells cultured on-chip form dense microvilli under dynamic flow and reconstitute the expression and physiological localization of key membrane transport proteins, such as nutrient and drug efflux transporters, that are critical to the barrier function of the placenta. We have leveraged this platform to study maternal-fetal transport. Our initial proof-of-principle studies centered around reconstituting physiological glucose transfer on-chip. We have built upon this work by utilizing this platform to investigate drug transfer across the placental barrier. Using the gestational diabetes drug glyburide as a model compound, we demonstrate that efflux transporter-mediated active transport function of the human placental barrier is reconstituted on-chip, thereby limiting fetal exposure to maternally administered drugs. The placenta-on-a-chip system represents an important advance in the development of new technologies to model and study the physiological complexity of the human placenta. In particular, our work demonstrates the potential for the placenta-on-a-chip to be used as a screening platform to more accurately predict drug transport across the placenta in pregnancy.
Cassidy Blundell– PhD student, University of Pennsylvania, Philadelphia, PA
University of Pennsylvania
Cassidy Blundell is a bioengineering PhD student in the HHMI-NIBIB Interfaces program at the University of Pennsylvania. She is advised by Dr. Dan Huh and has worked to develop the placenta-on-a-chip, a microphysiological model of the human placental barrier, an enabling tool for placental biology research. Cassidy holds a B.S. in biomedical engineering from Boston University.