A team of investigators including scientists of the National Institutes of Health, and the Wayne State University School of Medicine/Detroit Medical Center, have developed a “placenta-on-a-chip” to study the inner workings of the human placenta and its role in pregnancy.
The device imitates, on a micro-level, the structure and function of the human placenta and models the transfer of nutrients from mother to fetus.
Their study, “Placenta-on-a-Chip: A novel platform to study the biology of the human placenta,” was published online in the Journal of Maternal-Fetal & Neonatal Medicine.
“We believe that this system may be used to address questions that are difficult to answer with the current placenta model systems and serve to enable research in pregnancy and its complications,” said Roberto Romero, M.D., D.Med.Sci., chief of the Perinatology Research Branch, professor at the Center for Molecular Medicine and Genetics at Wayne State University, and an attending physician at the Detroit Medical Center.
The device, which can be used repeatedly in multiple experiments, may reduce the cost of placental research by replacing the use of animal models in medical studies. The prototype is the latest in a series of “organ-on-a-chip” technologies developed to accelerate biomedical advances.
The placenta is a temporary organ that develops in pregnancy. It serves as the major interface between mother and fetus. Among its many functions, the placenta acts as a “crossing guard” for substances transmitted between mother and fetus. The placenta helps nutrients and oxygen move to the fetus and helps waste products move away. It also attempts to halt harmful environmental exposures like bacteria, viruses and certain medications, from reaching the fetus.
Researchers are trying to learn how the placenta manages all of these functions, knowledge that is expected to help clinicians better assess placental health and improve pregnancy outcome. However, studying the placenta in humans presents challenges. Such studies are time-consuming, subject to a great deal of variability and carry potential risk for the fetus. Previous studies on placental transport have relied largely upon the use of animal models and laboratory-grown human cells. While those methods have yielded helpful information, Dr. Romero said, they have important limitations in replicating normal physiological processes in humans.
The placenta-on-a-chip consists of two small channels separated by a thin membrane made of extracellular matrix. Fetal endothelial cells are seeded into one side of the membrane, and maternal cells on the other. The chip mimics the placental barrier, where oxygen and nutrients are delivered to the growing baby and the waste products are removed from the baby’s blood critical to prenatal health. The placental barrier also controls the transport of potentially harmful pathogens between the mother and fetus.
After designing the structure of the model, the researchers tested its function by evaluating the transfer of glucose (a substance made by the body when converting carbohydrates to energy) from the maternal compartment to the fetal compartment. The successful glucose transfer in the device mirrored what occurs in the human body.
The development of such chips allows researchers to test the effect of drugs now in development and to ask and test fundamental biological questions, said Amar Basu, Ph.D., associate professor of WSU Electrical and Computer Engineering and Biomedical Engineering, and Mark Ming-Cheng Cheng, Ph.D., associate professor of WSU Electrical and Computer Engineering and director of the Nanofabrication Core. The pair collaborate with researchers in the PRB on placenta-on-a-chip production and advancement.
One challenge in medicine is the lack of cell and tissue models that recreate the environment in the body. Drugs and other therapies are often tested on cells layered in petri dishes, but such models do not accurately reflect the body’s complex environment, which includes three-dimensional connective matrix, multilayer structures and physical stimuli such as mechanical stress and temperature, Drs. Basu and Cheng explained. As a result, therapies that appear effective in the lab environment often fail during animal or human trials. Organ-on-a-chip systems mimic the microstructures and microenvironment in the body. For patients, this will ultimately translate into better therapies and a more rapid development pipeline. In the future, organs-on-a-chip may be synthesized directly from patient samples, which will verify personalized treatments for an individual.
“The chip may allow us to do experiments more efficiently and at a lower cost than animal studies,” said Dr. Romero. “With further improvements, we hope this technology may lead to the better understanding of normal placental processes and placental disorders.”
Dr. Romero said the placenta-on-a-chip was developed with the contributions of physicians and scientists from the Seoul National University and Asan Medical Center in South Korea, and Dr. Dongeon Huh of the University of Pennsylvania.
The device is the result of collaboration between medical researchers and those working in electrical and biomedical engineering.
“The transdisciplinary work between the College of Engineering and the School of Medicine allowed for rapid prototyping of microfluidic/bio-microsystems for organ-on-a-chip,” said Farshad Fotouhi, Ph.D., dean of the WSU College of Engineering. “Our engineering faculty have experience in micro and nano fabrication, including those incorporating living systems.”
“The placenta-on-a-chip platform represents a remarkable new methodology and model to study the role and biology of the human placenta,” said Jack D. Sobel, M.D., dean of the WSU School of Medicine and a researcher in obstetrics and gynecology. “In the past, our knowledge of placental function was limited by reliance on animal models and in vitro systems did not have sufficient physiologic basis. The miniaturized placenta-on-a-chip offers ready access to perform legitimate biologic experiments that will provide insight into the workings of the placenta. I am delighted that WSU faculty have participated in the development of this new model.”
“It's a sad fact that annually, infant mortality claims the lives of millions of infants and children across the globe," said Joe Mullany, chief executive officer of the Detroit Medical Center. "The DMC is proud to join our partners, NIH and Wayne State University to address this through the great research and collaboration of the placenta-on-a-chip study, which gives the world hope that one day we will reduce, and possibly even eradicate, adverse pregnancy outcomes.”