Placenta-on-a-Chip Technology Enhances Study Of Fetal Circulation

Dan Dongeun Huh, Ph.D. Wilf Family Term Chair & Assistant Professor Department of Bioengineering University of Pennsylvania Philadelphia, PA 19104 MedicalResearch.com Interview with:
Dan Dongeun Huh, Ph.D.
Wilf Family Term Chair & Assistant Professor
Department of Bioengineering
University of Pennsylvania
Philadelphia, PA 19104

Medical Research: What is the background for this study? What are the main findings?

Response: The placenta is a temporary organ central to pregnancy and serves as a major interface that tightly regulates transport of various endogenous and exogenous materials between mother and fetus. The placental barrier consisting of the closely apposed trophoblast epithelium and fetal capillary endothelium is responsible for maintaining this critical physiological function, and its dysfunction leads to adverse pregnancy outcomes. Despite its importance, barrier function of the placenta has been extremely challenging to study due to a lack of surrogate models that faithfully recapitulate the key features of the placental barrier in humans. Our study aims to directly address this long-standing technical challenge by providing a microengineered in vitro system that replicates architecture, microenvironment, and physiological function of the human placenta barrier. This “placenta-on-a-chip” device consists of microfabricated upper and lower cell culture chambers separated by a thin semipermeable membrane, and the placental barrier is generated by culturing human trophoblasts and fetal endothelial cells on either side of the membrane with steady flows of culture media in both chambers. This microfluidic cell culture condition allowed the cells to form confluent monolayers on the membrane surface and to create a bi-layer tissue that resembled the placental barrier in vivo. Moreover, the microengineered barrier enabled transport of glucose from the maternal chamber to the fetal compartment at physiological rates.


Medical Research: What should clinicians and patients take away from your report?

Response: This study suggests an exciting possibility to utilize microengineering technologies to address major limitations of existing placenta models based on traditional cell culture, perfused whole placenta, and animals. Our placenta-on-a-chip system provides unprecedented capabilities to simulate, visualize, and quantitatively analyze the placental barrier and its critical transport functions. We believe that our model holds great potential as a novel enabling platform for the study of placental barrier function and other important physiological processes in the placenta.

Medical Research: What recommendations do you have for future research as a result of this study?

Response: It is exciting to think about the possibility of using our microengineered model and other similar platforms not only for the study of placental biology but also for drug screening applications. Our approach allows for continuous monitoring and quantitative analysis of drug transport from the intervillous space to the fetal circulation, and this new capability can be leveraged in understanding fetal exposure to drugs or exploring drug dosing for prenatal treatment. Another exciting possibility for future research is to use our ability to precisely control and manipulate cells and their microenvironment to develop disease models and study placental dysfunction in various pathological contexts.

Citation:

Ji Soo Lee, Roberto Romero, Yu Mi Han, Hee Chan Kim, Chong Jai Kim, Joon-Seok Hong, Dongeun Huh. Placenta-on-a-chip: a novel platform to study the biology of the human placenta. The Journal of Maternal-Fetal & Neonatal Medicine, 2015; 1 DOI: 10.3109/14767058.2015.1038518

Dan Dongeun Huh, Ph.D., Wilf Family Term Chair & Assistant Professor, Department of Bioengineering, & University of Pennsylvania (2015). Placenta-on-a-Chip Technology Enhances Study Of Fetal Circulation