ArticleStem cell research & therapy2025
Apoptotic vesicles of mesenchymal stem cells promote M2 polarization and alleviate early-onset preeclampsia via miR-191-5p.
Article in Stem cell research & therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Integration of angiogenic pathway-related proteomics and clinical features via ensemble learning for precision risk stratification of early-onset preeclampsia.European journal of obstetrics & gynecology and reproductive biology: X · 2026Article
- Integrative single-cell and machine learning analysis identifies a tumor doubling time-related prognostic signature and therapeutic targets in head and neck squamous cell carcinoma.Translational oncology · 2026Article
- Integrative single-cell and spatial transcriptomics analysis reveals a baicalein-responsive 10-gene signature for non-small cell lung cancer.Translational oncology · 2026Article
- Therapeutic potential of mesenchymal stem cell-derived apoptotic vesicles in liver fibrosis: targeting the IGFBP3/PI3K-AKT axis via miR-409-3p.Stem cell research & therapy · 2026Article
- Apoptotic-mimetic nanovesicles orchestrate immune-vascular-osteogenic crosstalk for critical-sized craniofacial bone regeneration.Materials today. Bio · 2026Article
- Single-cell analysis of TIGD genes in hepatocellular carcinoma: Prognostic value and functional characterization.Translational oncology · 2026Article
- Mesenchymal stem/stromal cell-based therapies for autism spectrum disorder: emerging evidence and clinical prospects.Journal of translational medicine · 2026Review
- Exosomes in hypertension: mechanisms, biomarkers, and therapeutic opportunities.Frontiers in immunology · 2026Review
- AJUBA: The Master Regulator Bridging EMT and Immune Evasion in Colorectal Cancer.Mediators of inflammation · 2026Article
- Therapeutic potential of stem cell-derived extracellular vesicles in aging and regeneration.Frontiers in aging · 2026Review
- PDGFRβ in Stem Cell Microenvironments: Cross-Tissue Evidence and Hypotheses for the Limbal Stem Cell Niche.Stem cells international · 2026Review
- Serglycin's role in primary liver cancer: insights into tumor microenvironment and macrophage interaction.Frontiers in immunology · 2025Article
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6 authors.
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Abstract
backgroundMacrophages play a crucial role in the development of early-onset preeclampsia (EOPE), which may be closely associated with an imbalance in macrophage M1/M2 polarization. Mesenchymal stem cell (MSC)-derived apoptotic vesicles (apoVs) have anti-inflammatory, tissue repair, and immunomodulatory functions. MSC-apoVs may ameliorate EOPE by regulating macrophage polarization, but the underlying mechanisms remain to be clarified.
methodsMacrophage infiltration and M1/M2 polarization were first analyzed in the placentas of PE patients and normal pregancies to identify macrophage alterations in EOPE placentas. MSC-apoVs were extracted and characterized. The effects of MSC-apoVs on macrophage polarization and trophoblasts invasion were validated in vivo and in vitro. miRNA transcriptomic sequencing of MSC-apoVs was conducted to identify key miRNAs involved in macrophage M2 polarization and to investigate upstream and downstream regulation factors, which were further validated in vivo and in vitro.
resultsThe proportion of M2 macrophages was significantly reduced in EOPE placentas. MSC-apoVs carrying high levels of miR-191-5p recruited macrophages, downregulated CDK6 protein expression, stabilized mitochondrial membrane potential (MMP), and promoted M2 polarization of macrophages. This enhanced the invasion of trophoblasts and improved EOPE pregnancy outcomes in mice, including reduced blood pressure, decreased urine protein, and improved embryo quality. Overexpression of miR-191-5p mimics in MSC-apoVs further alleviated EOPE-related symptoms, whereas inhibition of miR-191-5p reduced the therapeutic effect of MSC-apoVs. Further experiments confirmed that M2 macrophages polarized by MSC-apoVs promote trophoblasts invasion by secreting platelet-derived growth factor-AB (PDGF-AB), which binds to platelet-derived growth factor receptor-beta (PDGFR-β) on trophoblasts, directly activating the downstream PI3K-AKT-mTOR signaling pathway, thereby improving EOPE.
conclusionOur findings reveal the crucial role of M2 macrophages in the pathogenesis of EOPE. MSC-apoVs with high miR-191-5p recruit macrophages, downregulate CDK6, stabilize MMP, and promote M2 polarization, increasing PDGF-AB secretion, which enhances trophoblasts invasion and thereby treat EOPE. Therefore, MSC-apoVs therapy may serve as a promising strategy to improve the prognosis of EOPE.
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