Editors' ChoicePregnancy

Organs-on-chips take baby steps

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Science Translational Medicine  15 May 2019:
Vol. 11, Issue 492, eaax1713
DOI: 10.1126/scitranslmed.aax1713

Abstract

Two organ-on-chip devices enable investigation of cellular interactions in human fetal membranes in vitro.

During pregnancy, the fetus is enclosed within membranes that, if ruptured, can cause preterm birth or other complications. The factors that maintain fetal membranes, and those that can disrupt it, are poorly understood because intact membranes are difficult to obtain and preserve. Fetal membranes consist of multiple cell types that work together to maintain tissue structure. Thus, to accurately study fetal membranes in vitro, different cell types must be grown in close proximity but ideally in distinct chambers so that chemical factors—such as hormones or drugs—can be controllably added to each cell type.

In a pair of papers, Richardson et al. fabricated microfluidic fetal membrane organ-on-chip devices. In the first study, their device consisted of top and bottom chambers separated by a semipermeable, synthetic membrane. They seeded human cells isolated from the amnion—the innermost fetal membrane—in the top chamber, and cells isolated from the decidua—the thick membrane that lines the uterus—in the bottom chamber. In the second study, two types of amnion-derived cells were seeded into separate chambers connected by microfluidic channels filled with extracellular matrix that was easily remodeled by the cells. Collectively, these two devices enabled the researchers to closely monitor behaviors (signaling, migration) of cells isolated from fetal membranes when grown alone or with another cell type, during homeostatic conditions and under oxidative stress. Their results suggest that these cells are influenced by both neighboring cells and their environment, providing new insights into the individual and collective roles of the cells in fetal membranes.

Although these devices are a step forward in studying these important structures, they still only consist of two cell types and thus are very simplistic compared with native fetal membranes. Furthermore, important physical factors were neglected, such as shear stress from amniotic fluid or membrane stretching. However, particularly when seeded with human cells, these types of devices will enable studies to help elucidate the physiology of fetal membranes, determine how different genetic and environmental stresses contribute to their rupture, and identify new molecules that can protect them to prevent preterm birth.

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