Articles
Vol. 69 No. 4 (2025)
Placental mesenchymal stem cell exosomes drive macrophage M2 polarization via the miR-146a-5p/TRAF6 axis to ameliorate preeclampsia
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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Published: 17 November 2025
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The functional state of placental mesenchymal stem cells (PMSCs) plays a critical role in maintaining maternal-fetal interface homeostasis during the pathogenesis of preeclampsia (PE). Given the limitations associated with direct stem cell transplantation, this study aimed to investigate the therapeutic potential of PMSC-derived exosomes and their carried miR-146a-5p. Clinical sample analysis revealed a significant downregulation of miR-146a-5p in placental tissues from PE patients, accompanied by impaired proliferation, migration, and angiogenic dysfunction of PMSCs. In an in vitro model, exosome intervention effectively reversed hypoxia-induced trophoblast cell apoptosis and enhanced migratory capacity. Furthermore, it promoted macrophage polarization towards the anti-inflammatory M2 phenotype and markedly improved the inflammatory cytokine secretion profile. In a PE mouse model, exosome treatment reduced maternal blood pressure and proteinuria levels, alleviated fetal growth restriction, and up-regulated the expression of M2 macrophage markers in placental tissue. Mechanistically, miR-146a-5p targeted TRAF6 to suppress NF-κB pathway activation, an effect that could be reversed by specific inhibitors. This study is the first to demonstrate that PMSC-derived exosomes, via the miR-146a-5p/TRAF6 axis, concurrently ameliorate trophoblast dysfunction and correct macrophage polarization imbalance. The efficient intercellular delivery of miR-146a-5p by exosomes underscores their potential as a novel targeted therapeutic strategy for PE.
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Ethics Approval
this study was approved by the Ethics Committee of Chongqing Maternal and Child Health Care HospitalSupporting Agencies
Natural Science Foundation of ChongqingHow to Cite
1.
Liu X, Li R, Sun J, Yang Y, Hu L. Placental mesenchymal stem cell exosomes drive macrophage M2 polarization via the miR-146a-5p/TRAF6 axis to ameliorate preeclampsia. Eur J Histochem [Internet]. 2025 Nov. 17 [cited 2025 Dec. 26];69(4). Available from: https://www.ejh.it/ejh/article/view/4426
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