Placenta-on-a-chip: a novel platform to study the biology of the human placenta

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.

A microphysiological model of the human placental barrier

“…For each group, barrier function was quantified by the percent increase in fetal glucose concentration over the period of perfusion. Additionally, the percent rate of transfer was calculated for the co-culture model using the following equation previously described in placental transport studies 19 ,…”

Placental origins of adverse pregnancy outcomes: potential molecular targets: an Executive Workshop Summary of the Eunice Kennedy Shriver National Institute of Child Health and Human Development

“…The application of newer organ on chip technology could allow the testing of potential interventions identified during atlas construction. 430 Real-time approaches will require either new imaging modalities, or be “omics” in nature. As discrete markers of placental function linked to specific disease phenotypes emerge, it may be possible to reduce the processing from a minimum of a laboratory work day to less than a few hours, providing near real time feedback for non-imaging modalities.…”

Multisensor-integrated organs-on-chips platform for automated and continual in situ monitoring of organoid behaviors

“…To this end, the recently emerged organ-on-a-chip systems that combine advanced microfluidic technologies and tissue engineering approaches to simulate both the biology and physiology of human organs have been developed (8,(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30). These miniaturized human organ models have several advantages over conventional models, such as more accurate prediction of human responses and, in particular, multiorgan interactions when different organ modules are assembled in a single fluid circuit (7,31).…”