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SELECTBIO Conferences Circulating Biomarkers and Extracellular Vesicles Europe 2023


Modeling the Feto-Maternal Communication by Extracellular Vesicles using Intrauterine Tissue Microphysiologic System

Ramkumar Menon, Professor, The University of Texas Medical Branch (UTMB)

The fetal inflammatory response in response to intrauterine inflammation is a major determinant of adverse pregnancy outcomes, specifically preterm birth (PTB). Inflammation causes intrauterine tissue (fetal membrane/amniochorion) senescence and generate damage-associated molecular pattern markers (e.g., High mobility group box 1 protein [HMGB1]). HMGB1 is released via extracellular vesicles. We tested the hypothesis that exosomal HMGB1 is one of the fetal signals capable of increasing Feto-Maternal interface (FMi) inflammation, predisposing to PTB. To test this hypothesis, exosomes from amnion epithelial cells (AECs) from the intrauterine fetal membranes grown under normal conditions were engineered to contain HMGB1 by (eHMGB1). eHMGB1 was characterized, and its propagation through FMi was tested using a four-chamber microfluidic organ-on-a-chip device (FMi-OOC) that contained four distinct cell types (amnion epithelium, amnion mesenchyme, chorion trophoblast and decidual cells) connected through microchannels. eHMGB1 propagated through the fetal cells to the maternal decidua and increased inflammation associated with PTB. To physiologically validate this finding, eHMGB1(containing 10 ng) was intra-amniotically injected into CD-1 mice on embryonic day 17 which resulted in PTB. In vivo kinetics was determined by injecting carboxyfluorescein succinimidyl ester labeled eHMGB1. We report that eHMGB1 trafficking in mice causing PTB was associated with increased FMi inflammation. Our study determined that fetal exosome-mediated paracrine signaling can generate inflammation and induce parturition.

Add to Calendar ▼2023-06-19 00:00:002023-06-20 00:00:00Europe/LondonCirculating Biomarkers and Extracellular Vesicles Europe 2023Circulating Biomarkers and Extracellular Vesicles Europe 2023 in Rotterdam, The NetherlandsRotterdam, The