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

Ramin Khanabdali, Aida Shakouri-Motlagh, Sarah Wilkinson, Padma Murthi, Harry M. Georgiou, Shaun P. Brennecke, Bill Kalionis

Research output: Contribution to journalArticleResearchpeer-review

2 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1215-1225
Number of pages11
JournalJournal of Molecular Medicine
Volume96
Issue number11
DOIs
Publication statusPublished - 1 Nov 2018

Keywords

  • Aspirin
  • Decidua
  • Mesenchymal stem/stromal cells
  • Preeclampsia

Cite this

@article{5513827eb7d54757a7877874be596986,
title = "Low-dose aspirin treatment enhances the adhesion of preeclamptic decidual mesenchymal stem/stromal cells and reduces their production of pro-inflammatory cytokines",
abstract = "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.",
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Low-dose aspirin treatment enhances the adhesion of preeclamptic decidual mesenchymal stem/stromal cells and reduces their production of pro-inflammatory cytokines. / Khanabdali, Ramin; Shakouri-Motlagh, Aida; Wilkinson, Sarah; Murthi, Padma; Georgiou, Harry M.; Brennecke, Shaun P.; Kalionis, Bill.

In: Journal of Molecular Medicine, Vol. 96, No. 11, 01.11.2018, p. 1215-1225.

Research output: Contribution to journalArticleResearchpeer-review

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

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U2 - 10.1007/s00109-018-1695-9

DO - 10.1007/s00109-018-1695-9

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