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DOI: 10.1055/s-0040-1715166
Mesenchymal Stem Cells Attenuate Lipopolysaccharide-Induced Inflammatory Response in Human Uterine Smooth Muscle Cells
Funding The study was supported from the Department of Obstetrics, Gynecology, and Reproductive Sciences, UTHealth-McGovern Medical School, Houston TX and The Larry C. Gilstrap, MD, Center for Perinatal and Women's Health Research, University of Texas Health Science Center at Houston.
Abstract
Objective The aim of this study was to determine if mesenchymal stem cells (MSCs) would suppress the inflammatory response in human uterine cells in an in vitro lipopolysaccharide (LPS)-based preterm birth (PTB) model.
Study Design Cocultures of human uterine smooth muscle cells (HUtSMCs) and MSCs were exposed to 5 μg/mL LPS for 4 hours and further challenged with 1 μg/mL LPS for a subsequent 24 hours. Key elements of the parturition cascade regulated by toll-like receptors (TLRs) through activation of mitogen-activated protein kinases (MAPKs) were quantified in culture supernatant as biomarkers of MSC modulation.
Results Coculture with MSCs significantly attenuated TLR-4, p-JNK, and p- extracellular signal-regulated kinase 1/2 (ERK1/2) protein levels compared with HUtSMCs monoculture (p = 0.05). In addition, coculture was associated with significant inhibition of proinflammatory cytokines interleukin (IL)-6 and IL-8 (p = 0.0001) and increased production of anti-inflammatory cytokines IL-10 and transforming growth factor (TGF)-β1 (p = 0.0001).
Conclusion MSCs appear to play a role in significantly attenuating LPS-mediated inflammation via alteration of down-stream MAPKs. MSCs may represent a novel, cell-based therapy in women with increased risk of inflammatory-mediated preterm birth.
Keywords
mesenchymal stem cells - lipopolysaccharide - inflammatory response - cytokines - preterm birthNote
This study was presented as Posters at the 38th Annual Meeting of the Society for Maternal-Fetal Medicine; January 29 to February 3, 2018; Dallas, TX, and at the 65th Annual Scientific Meeting of the Society for Reproductive Investigation; March 6 to 10, 2018 in San Diego, CA.
Publikationsverlauf
Eingereicht: 27. März 2020
Angenommen: 24. April 2020
Artikel online veröffentlicht:
23. September 2020
© 2020. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).
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