Low-dose aspirin treatment enhances the adhesion of preeclamptic decidual mesenchymal stem/stromal cells and reduces their production of pro-inflammatory cytokines.

Abstract

Preeclampsia (PE) is a hypertensive disorder of human pregnancy. Low-dose aspirin (acetylsalicylic acid) (60-150mg/day) is used to prevent PE when taken early in pregnancy. The effect of aspirin on term PE remains uncertain. Abnormal placentation is a hallmark of PE and leads to increased placental oxidative stress, which triggers the release of anti-angiogenic factors that cause local damage to the decidual vasculature. The damage subsequently spreads systemically and culminates in maternal clinical symptoms. Decidua basalis mesenchymal stem/stromal cells (DMSCs) reside in a vascular microenvironment. In PE, DMSCs are exposed to abnormally high levels of oxidative stress and circulating inflammatory factors from the maternal blood. We previously showed that colony-forming unit ability and resistance to oxidative stress in DMSCs are reduced in MSCs derived from term PE pregnancies (PE-DMSCs). The action, if any, of aspirin on term PE-DMSCs has not been reported. In this study, aspirin (5μg/mL) was found to significantly increase PE-DMSC adhesion compared to untreated PE-DMSCs and gestation-matched control DMSCs (p value < 0.001) but had no effect on PE-DMSC proliferation. ELISA analysis showed that aspirin significantly decreased the production of inflammatory cytokines IFN-γ (p value < 0.05) and IL-8 (p value < 0.001) in PE-DMSCs. In addition, aspirin treatment increased the antioxidant capacity of PE-DMSCs compared with the untreated group (p value < 0.05). This study is the first to reveal a novel, beneficial action of aspirin on PE-DMSCs from term PE pregnancies by improving their adhesion, suppressing their production of pro-inflammatory cytokines production, and increasing their antioxidant capacity. KEY MESSAGES: Preeclampsia (PE) is a serious hypertensive disorder of pregnancy. The risk of PE is reduced by aspirin but the mechanism is poorly understood. Decidua basalis mesenchymal stem/stromal cells (DMSCs) are abnormal in PE. Aspirin treatment improves multiple functions of PE-DMSCs. Improved DMSC function may contribute to the beneficial effect of aspirin.