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The device was designed to imitate, on a micro-level, the structure and function of the placenta and model the transfer of nutrients from mother to fetus. Image credit: Business Insider

Placenta-on-a-chip

National Institutes of Health (NIH) researchers and their colleagues have developed a "placenta-on-a-chip" to study the inner workings of the human placenta and its role in pregnancy.

The device was designed to imitate, on a micro-level, the structure and function of the placenta and model the transfer of nutrients from mother to fetus. This prototype is one of the latest in a series of organ-on-a-chip technologies developed to accelerate biomedical advances.

The study, published online in the Journal of Maternal-Fetal & Neonatal Medicine, was conducted by an interdisciplinary team of researchers from the NIH's Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the University of Pennsylvania, Wayne State University/Detroit Medical Center, Seoul National University and Asan Medical Center in South Korea.

"We believe that this technology may be used to address questions that are difficult to answer with current placenta model systems and help enable research on pregnancy and its complications."

Roberto Romero, M.D., chief of the NICHD's Perinatology Research Branch, and one of the study authors.

The placenta is a temporary organ that develops in pregnancy and is the major interface between mother and fetus. Among its many functions is to serve as a "crossing guard" for substances traveling between mother and fetus. The placenta helps nutrients and oxygen move to the fetus and helps waste products move away. At the same time, the placenta tries to stop harmful environmental exposures, like bacteria, viruses and certain medications, from reaching the fetus. When the placenta doesn't function correctly, the health of both mom and baby suffers.

Researchers are trying to learn how the placenta manages all this traffic, transporting some substances and blocking others. This knowledge may one day help clinicians better assess placental health and ultimately improve pregnancy outcomes.

However, studying the placenta in humans is challenging: it is time-consuming, subject to a great deal of variability and potentially risky for the fetus. For those reasons, previous studies on placental transport have relied largely on animal models and on laboratory-grown human cells. These methods have yielded helpful information, but are limited as to how well they can mimic physiological processes in humans.

Researchers created the placenta-on-a-chip technology to address these challenges, using human cells in a structure that more closely resembles the placenta's maternal-fetal barrier. The device consists of a semi-permeable membrane between two tiny chambers, one filled with maternal cells derived from a delivered placenta and the other filled with fetal cells derived from an umbilical cord.

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 transfer of glucose in the device mirrored what occurs in the body.

"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 better understanding of normal placental processes and placental disorders."

Abstract
Objective: Studying the biology of the human placenta represents a major experimental challenge. Although conventional cell culture techniques have been used to study different types of placenta-derived cells, current in vitro models have limitations in recapitulating organ-specific structure and key physiological functions of the placenta. Here we demonstrate that it is possible to leverage microfluidic and microfabrication technologies to develop a microengineered biomimetic model that replicates the architecture and function of the placenta.

Materials and methods: A “Placenta-on-a-Chip” microdevice was created by using a set of soft elastomer-based microfabrication techniques known as soft lithography. This microsystem consisted of two polydimethylsiloxane (PDMS) microfluidic channels separated by a thin extracellular matrix (ECM) membrane. To reproduce the placental barrier in this model, human trophoblasts (JEG-3) and human umbilical vein endothelial cells (HUVECs) were seeded onto the opposite sides of the ECM membrane and cultured under dynamic flow conditions to form confluent epithelial and endothelial layers in close apposition. We tested the physiological function of the microengineered placental barrier by measuring glucose transport across the trophoblast-endothelial interface over time. The permeability of the barrier study was analyzed and compared to that obtained from acellular devices and additional control groups that contained epithelial or endothelial layers alone.

Results: Our microfluidic cell culture system provided a tightly controlled fluidic environment conducive to the proliferation and maintenance of JEG-3 trophoblasts and HUVECs on the ECM scaffold. Prolonged culture in this model produced confluent cellular monolayers on the intervening membrane that together formed the placental barrier. This in vivo-like microarchitecture was also critical for creating a physiologically relevant effective barrier to glucose transport. Quantitative investigation of barrier function was conducted by calculating permeability coefficients and metabolic rates in varying conditions of barrier structure. The rates of glucose transport and metabolism were consistent with previously reported in vivo observations.

Conclusion: The “Placenta-on-a-Chip” microdevice described herein provides new opportunities to simulate and analyze critical physiological responses of the placental barrier. This system may be used to address the major limitations of existing placenta model systems and serve to enable research platforms for reproductive biology and medicine.

Read More: http://informahealthcare.com/doi/abs/10.3109/14767058.2015.1038518

The study, published online in the Journal of Maternal-Fetal & Neonatal Medicine, was conducted by an interdisciplinary team of researchers from the NIH's Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the University of Pennsylvania, Wayne State University/Detroit Medical Center, Seoul National University and Asan Medical Center in South Korea.

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