ArticleScientific reports2022
Extracellular vesicles derived from GMSCs stimulated with TNF-α and IFN-α promote M2 macrophage polarization via enhanced CD73 and CD5L expression.
Article in Scientific reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed.
- M2 polarization of macrophages: Manipulation of spinal cord injury repair.Neural regeneration research · 2026Article
- Applications and prospects of the immunomodulatory and regenerative capabilities of gingival mesenchymal stem cells for chronic inflammation treatment.Molecular biology reports · 2026Review
- Bioreactor-derived EVs from placental MSCs show context- and donor-specific immunomodulatory trends in human 3D lung inflammatory models.Stem cell research & therapy · 2026Article
- Nonunion After Ankle Arthrodesis: A Contemporary Review.Foot & ankle international · 2026Review
- Extracellular vesicles as therapeutic agents for retinal ganglion cell degeneration: current challenges and future prospects.International ophthalmology · 2026Review
- Impaired IL-35/Treg Axis Facilitates Neuropathic Pain Via TNF-α, TLR4, and HMGB1 Activation.Immunity, inflammation and disease · 2026Article
- Biomimetic nanovesicles and nanotechnology for oral and maxillofacial diseases.Discover nano · 2026Review
- The immunomodulatory power of mesenchymal stem/stromal cell-derived extracellular vesicles in bone disorders: A comprehensive review.Clinical and experimental medicine · 2026Review
- Mesenchymal Stromal/Stem Cell-Based Therapies for Liver Regeneration: Current Status and Future Directions.International journal of molecular sciences · 2026Review
- Extracellular vesicles for macrophage reprogramming: an emerging paradigm in immunomodulatory therapeutics.Journal of biological engineering · 2025Review
- Establishment of a prognostic model and immune profiling based on phagocytic regulatory genes in hepatocellular carcinoma.Translational cancer research · 2025Article
- Therapeutic potential of CD73Histology and histopathology · 2025Review
- Exosomes and MicroRNAs: key modulators of macrophage polarization in sepsis pathophysiology.European journal of medical research · 2025Review
- Functional heterogeneity of mesenchymal stem cells and their therapeutic potential in the K18-hACE2 mouse model of SARS-CoV-2 infection.Stem cell research & therapy · 2025Article
- Extracellular Vesicles in Periodontitis: Pathogenic Mechanisms and Therapeutic Potential.Journal of inflammation research · 2025Review
- Mesenchymal Stem Cell-Derived Exosomes: A Promising Therapeutic Strategy for Spinal Cord Injury.International journal of nanomedicine · 2025Review
- miRNA-431-5p enriched in EVs derived from IFN-β stimulated MSCs potently inhibited ZIKV through CD95 downregulation.Stem cell research & therapy · 2024Article
- High throughput screening of mesenchymal stromal cell morphological response to inflammatory signals for bioreactor-based manufacturing of extracellular vesicles that modulate microglia.Bioactive materials · 2024Article
- Review
- A novel role of CD73-IFNγ signalling axis in human mesenchymal stromal cell mediated inflammatory macrophage suppression.Regenerative therapy · 2024Article
Corrections and comments
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Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Immunoregulatory properties of mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) are promising. Gingival tissue-derived MSCs (GMSCs) have unique immunoregulatory capacity and secrete large amounts of EVs. Recent findings suggest that priming MSCs with inflammatory stimuli is an effective strategy for cell-free therapy. However, the precise mechanism by which the contents of EVs are customized has not been fully elucidated. Here, we show that EVs derived from GMSCs primed with a combination of two pro-inflammatory cytokines, tumor necrosis factor-α (TNF-α) and interferon-α (IFN-α), synergistically promote anti-inflammatory M2 macrophage polarization by increasing the expression of cluster of differentiation 73 (CD73) and CD5 molecule-like (CD5L). Expression of CD73 by TNF-α/IFN-α stimulation was transcriptionally upregulated by the activation of mammalian target of rapamycin signaling and nuclear translocation of hypoxia-inducible factor 1α in GMSCs. TNF-α/IFN-α treatment also significantly increased the expression of CD5L mRNA via the transcription factor DNA-binding protein inhibitor ID3 and liver X receptor. Interestingly, exosomal CD5L is a prerequisite for the synergistic effect of EVs-mediated M2 macrophage polarization. These results indicate that combined pre-licensing with TNF-α and IFN-α in GMSCs is ideal for enhancing the anti-inflammatory function of EVs, which contributes to the establishment of a therapeutic tool.
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