Mesenchymal Stem Cells Suppress Inflammatory Cytokines in Lipopolysaccharide Exposed Preterm and Term Human Pregnant Myometrial Cells

Abstract

Objective The objective of this study was to determine the cytokine response in human pregnant preterm and term myometrial cells exposed to lipopolysaccharide (LPS) and co-cultured with mesenchymal stem cells (MSCs). Study design Myometrium was obtained at cesarean delivery in term and preterm patients. Human myometrial cells were exposed to 5 μg/ml LPS for 4 hours (h) followed by 1 μg/ml LPS for 24 h and were co-cultured with MSCs for 24 h. Culture supernatants were collected at 24h and expression of cytokines, including IL-1β, IL-6, IL-8, TNF-α, TGF-β and IL-10, was quantified by ELISA. Results There was significantly increased expression of the pro-inflammatory cytokines IL-1β, IL-6, IL-8 and TNF-α in preterm myometrial cells treated with LPS compared to untreated preterm myometrial cells. Co-culture with MSCs significantly suppressed the pro-inflammatory cytokine levels in LPS treated preterm vs. treated term myometrial cells. Moreover, MSC co-cultured preterm myometrial cells expressed increased levels of the anti-inflammatory cytokines TGF-β and IL-10 compared to treated term myometrial cells. Conclusion MSCs ameliorate LPS-mediated inflammation in preterm human myometrial cells compared to term myometrial cells. Immunomodulatory effects of MSCs mediated through anti-inflammatory cytokine regulation suggest a potential cell-based therapy for preterm birth.