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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.