Testing of drugs using human feto-maternal interface organ-on-chips provide insights into pharmacokinetics and efficacy

Abstract

We developed multiple microfluidic organ-on-chip (OOC) devices that represent the structure, functions, and responses of the two feto-maternal interfaces (FMis) in humans (fetal membrane [FMi-OOC] and placenta [PLA-OOC]). Generated by BioRender.

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

“…To model the fetal membrane‐decidua FMi, a microfluidic in vitro device was designed and fabricated to mimic the in utero tissue. The FMi‐OOC used in the current study has been previously developed, tested, and validated 36,37,40,42–44 . Briefly, the device is composed of four concentric‐circle‐shaped culture compartments (one for maternal cells and three for fetal cells) interconnected through arrays of microfluidic channels to allow co‐cultivation communication among the four different cell types (Figure 1B).…”

“…Methods for obtaining and preparing cell-free collagen from amniotic membrane extracellular matrix (ECM) follow our previously reported procedure. 36,37,39,40 2.2.4 | Cell seeding in the FMi-OOC One day after the Matrigel coating, the devices were washed two times with complete DMEM-F12 medium before cell seeding. Immortalized cells (Figure 1D) were trypsinized and loaded into the FMi-OOC device, starting from the center chamber to the outside chamber (60 000 hFM_DEC cells for chamber 1; 200 000 hFM_CTCs + 5% primary collagen 49 + 25% Matrigel for chamber 2; 62 500 hFM_AMCs + 20% primary collagen + 25% Matrigel for chamber 3; and 120 000 hFM_AECs for chamber 4), similar to the concentration ratios seen in utero.…”

“…We used established immortalized cell lines from term, not in labor, human fetal membranes and decidua parietalis, as reported in our prior publications, [39][40][41] to be used in our FMi-OOC model (Figure 1A,B). Human maternal decidual cells (hFM_DEC) were cultured in DMEM/ F12 (Mediatech Inc., Manassas, VA, USA) supplemented with 10% FBS, 10% penicillin/streptomycin (Mediatech), and 10% amphotericin B (Sigma-Aldrich, Inc. St. Louis, MO).…”

“…The FMi-OOC used in the current study has been previously developed, tested, and validated. 36,37,40,[42][43][44] Briefly, the device is composed of four concentric-circle-shaped culture compartments (one for maternal cells and three for fetal cells) interconnected through arrays of microfluidic channels to allow co-cultivation communication among the four different cell types (Figure 1B). Chamber 1, the center chamber, contains maternal hFM_DECs, chamber 2 has fetal hFM_CTCs, chamber 3 has fetal hFM_AMCs, and the outermost chamber 4 is for fetal hFM_AECs.…”

Human-Based New Approach Methodologies in Developmental Toxicity Testing: A Step Ahead from the State of the Art with a Feto–Placental Organ-on-Chip Platform

“…Similarly, primary amnion epithelial and decidual cells were assembled in devices to recreate the feto–maternal interface [ 190 ]. A direct comparison of the feto–maternal interface OoC platform with other in vitro techniques (cell co-culture, transwell and placenta perfusion) has recently been discussed, highlighting the more physiological conditions provided by the OoC technology for barrier microfluidic studies [ 191 ]. None of these models included embryo/fetal cell types different from those directly facing the maternal side; however, some of them investigated adverse effects induced by exposure to nanoparticles [ 189 ], cadmium [ 192 ], cigarette smoke and dioxin [ 193 ].…”