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

TY - JOUR

T1 - Low-dose aspirin treatment enhances the adhesion of preeclamptic decidual mesenchymal stem/stromal cells and reduces their production of pro-inflammatory cytokines

AU - Khanabdali, Ramin

AU - Shakouri-Motlagh, Aida

AU - Wilkinson, Sarah

AU - Murthi, Padma

AU - Georgiou, Harry M.

AU - Brennecke, Shaun P.

AU - Kalionis, Bill

PY - 2018/11/1

Y1 - 2018/11/1

N2 - Abstract: Preeclampsia (PE) is a hypertensive disorder of human pregnancy. Low-dose aspirin (acetylsalicylic acid) (60–150 mg/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 (5 μg/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.

AB - Abstract: Preeclampsia (PE) is a hypertensive disorder of human pregnancy. Low-dose aspirin (acetylsalicylic acid) (60–150 mg/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 (5 μg/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.

KW - Aspirin

KW - Decidua

KW - Mesenchymal stem/stromal cells

KW - Preeclampsia

UR - http://www.scopus.com/inward/record.url?scp=85054308096&partnerID=8YFLogxK

U2 - 10.1007/s00109-018-1695-9

DO - 10.1007/s00109-018-1695-9

M3 - Article

VL - 96

SP - 1215

EP - 1225

JO - Journal of Molecular Medicine

JF - Journal of Molecular Medicine

SN - 0946-2716

IS - 11

ER -