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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

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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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Acknowledgements

We acknowledge the patients who consented to provide their placenta, and the clinical research midwives at the Royal Women’s Hospital, Sue Duggan and Moira Stewart for sample collection.

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Author notes

  1. Ramin Khanabdali and Aida Shakouri-Motlagh contributed equally to this work.

Authors and Affiliations

  1. Department of Maternal-Fetal Medicine Pregnancy Research Centre, The Royal Women’s Hospital, Parkville, Victoria, Australia

    Ramin Khanabdali, Aida Shakouri-Motlagh, Shaun P. Brennecke & Bill Kalionis

  2. Department of Obstetrics and Gynaecology, Melbourne Medical School, The University of Melbourne, Parkville, Victoria, Australia

    Ramin Khanabdali, Sarah Wilkinson, Harry M. Georgiou, Shaun P. Brennecke & Bill Kalionis

  3. Department of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia

    Padma Murthi

  4. The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia

    Padma Murthi

Authors
  1. Ramin Khanabdali
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  2. Aida Shakouri-Motlagh
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  3. Sarah Wilkinson
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  4. Padma Murthi
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  5. Harry M. Georgiou
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  6. Shaun P. Brennecke
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  7. Bill Kalionis
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Contributions

Ramin Khanabdali: Conception and design, collection and assembly of data, data analysis and interpretations, manuscript writing, and final approval of the manuscript.

Aida Shakouri-Motlagh: Conception and design, collection and assembly of data, data analysis and interpretations, and final approval of the manuscript.

Sarah Wilkinson: Collection and assembly of data and final approval of the manuscript.

Padma Murthi: Manuscript editing and final approval of the manuscript.

Harry M Georgiou: Manuscript editing and final approval of the manuscript.

Shaun P. Brennecke: Provision of study material or patients and final approval of the manuscript.

Bill Kalionis: Conception and design, data interpretations, manuscript writing, and final approval of the manuscript.

Corresponding author

Correspondence to Bill Kalionis.

Ethics declarations

The study was approved by the Human Research Ethics Committee of the Royal Women’s Hospital, Victoria, Australia.

Conflict of interest

The authors declare that they have no conflict of interest.

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Khanabdali, R., Shakouri-Motlagh, A., Wilkinson, S. et al. Low-dose aspirin treatment enhances the adhesion of preeclamptic decidual mesenchymal stem/stromal cells and reduces their production of pro-inflammatory cytokines. J Mol Med 96, 1215–1225 (2018). https://doi.org/10.1007/s00109-018-1695-9

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  • DOI: https://doi.org/10.1007/s00109-018-1695-9

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