Development of oxidative stress‐associated disease models using feto‐maternal interface organ‐on‐a‐chip

Abstract

Oxidative stress (OS) and inflammation arising from cellular derangements at the fetal membrane-decidual interface (feto-maternal interface [FMi]) is a major antecedent to preterm birth (PTB). However, it is impractical to study OS-associated FMi disease state during human pregnancy, and thus it is difficult to develop strategies to reduce the incidences of PTB. A microfluidic organ-on-chip model (FMi-OOC) that mimics the in vivo structure and functions of FMi in vitro was developed to address this challenge. The FMi-OOC contained fetal (amnion epithelial, mesenchymal, and chorion) and maternal (decidua) cells cultured in four compartments interconnected by arrays of microchannels to allow independent but interconnected co-cultivation. Using this model, we tested the effects of OS and inflammation on both fetal (fetal → maternal) and maternal (maternal → fetal) sides of the FMi and determined their differential impact on PTB-associated pathways. OS was induced using cigarette smoke extract (CSE) exposure. The impacts of OS were assessed by measuring cell viability, disruption of immune homeostasis, epithelial-to-mesenchymal transition (EMT), development of senescence, and inflammation. CSE propagated (LC/MS-MS analysis for nicotine) over a 72hour period from the maternal to fetal side, or vice versa. However, they caused How to cite this article: Richardson LS, Kammala AK, Kim S, et al. Development of oxidative stress-associated disease models using feto-maternal interface organ-on-a-chip. The

Endocrine-disrupting compounds and their impact on human placental function: evidence from placenta organ-on-chip studies

“…Sections of the array also contain blocks of PDMS to hold up the entire ceiling and prevent inadvertent collapse during the microfabrication process. The length of the cell chambers ranges from 1000–7000 μm, and all chambers had a height of 250 μm – in accordance with previously established dimensions in other devices 21,36–41 as well as based on existing knowledge on the volumes and surface areas of these cell layers in histological and microscopic sections of the placenta. 42–44 The microchannels lie in between these structures interconnecting the chambers.…”

“…S1A†). 21,34–41 Along with cellularity, the 2TPLA-OOC models the second-trimester hyperoxic oxygen tension and hormonal production.…”

“…The microfabrication procedure is similar to that described previously for multiple feto-maternal interface chips. 21,36–41 In short, to form the master mold, a two-step photolithography process was conducted. Briefly, the master mold was created using photosensitive epoxy (SU-8; MicroChem, Westborough, MA, USA) forming the first microchannel layer (5 μm-deep microchannels) and the second cell culture chamber layer (250 μm-deep cell culture chambers).…”

“…Dye propagation was done utilizing 3000 kDa Dextran beads (2.48 nm) (D3305, Invitrogen, Waltham, MA). We chose 3000 kDa Dextran beads as they are a standard size across our multiple chip platforms 21,36,37,39,40 so we can compare media diffusion rates across different systems. Additionally, many biological molecules, such as protein complexes or large infectious molecules, are around 3000 kDa, giving us a point of reference for when the media, rather than cells alone, is starting to propagate those components.…”