ArticleStem cell research & therapy2025
In-vitro immunomodulatory efficacy of extracellular vesicles derived from TGF-β1/IFN-γ dual licensed human bone marrow mesenchymal stromal cells.
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 14 papers.
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Who cites it
14 citing papers in PubMed.
- Advancing Sports Injury Treatment Through Cell-Free MSC-Based Therapies: A Narrative Review.Muscles (Basel, Switzerland) · 2026Review
- Gellan Gum Fluid Gel System for Controlled-Delivery of Cytokine-Licensed MSC-EVs to Enhance Corneal Repair in Limbal Stem Cell Deficiency.Advanced healthcare materials · 2026Article
- Extracellular vesicles and their cargo molecules for peripheral nerve injuries and neuropathies: The composition, properties, and impact.Molecular aspects of medicine · 2026Review
- The New Spine of Access to the Brain's Secrets: Extracellular Vesicles from Cerebrospinal Fluid Liquid Biopsies in CNS Diseases and Blood-Brain Barrier Research.Molecular neurobiology · 2026Review
- Matrix Bound Nanovesicles Modulatory Effect of Inflammation In Vitro in THP-1 Cells.Pharmaceutics · 2026Article
- Tonsil‑derived mesenchymal stem cell‑derived extracellular vesicles suppress MAPK‑NF‑κB signaling and restore osteogenic differentiation in LPS‑stimulated periodontal ligament fibroblasts.Molecular medicine reports · 2026Article
- Immune-evasive stem cells: engineering tolerance and reprogramming microenvironments for regenerative therapy.Stem cell research & therapy · 2026Review
- Quantitative evaluation of mesenchymal stromal cell immunomodulatory potency and cost-effectiveness of cytokine licensing for translational application.Journal of translational medicine · 2026Article
- Mesenchymal Stromal/Stem Cell-Based Therapies for Liver Regeneration: Current Status and Future Directions.International journal of molecular sciences · 2026Review
- Mesenchymal stem cell-derived extracellular vesicles in musculoskeletal regeneration: mechanisms, applications, and future prospects.Stem cell research & therapy · 2026Review
- Extracellular vesicle-mediated immunomodulation and targeted delivery: breakthroughs and challenges in rheumatoid arthritis therapy.Frontiers in immunology · 2026Review
- An updated review on the role of extracellular vesicles in immune system modulation in breast cancer with special emphasis on immune checkpoint regulators.Frontiers in immunology · 2026Review
- From pathogenesis to therapy: extracellular vesicles in osteoarthritis.Frontiers in bioengineering and biotechnology · 2026Review
- Mitochondrial Extracellular Vesicles: A Novel Approach to Mitochondrial Quality Control.Biomolecules · 2025Review
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Authors and funding
7 authors.
Funding
Abstract
backgroundMesenchymal stromal cells (MSCs) possess strong immunomodulatory properties, making them attractive candidates for regenerative medicine and immune-related therapies. Pre-activation, or licensing, of MSCs with cytokines such as interferon-gamma (IFN-γ) and transforming growth factor-beta 1 (TGF-β1) has been shown to enhance their immunosuppressive efficacy. Recent attention has turned to extracellular vesicles (EVs) released by licensed MSCs as a cell-free therapeutic alternative.
methodsSmall EVs were isolated from MSCs licensed with a combination of IFN-γ and TGF-β1. These EVs were characterized according to standardized criteria. Their immunomodulatory effects were assessed in vitro using two human immune models: a THP-1-derived macrophage polarization system and a peripheral blood mononuclear cell (PBMC) co-culture assay. Pro/anti-inflammatory molecules secretion, T cell proliferation, and regulatory T cell induction were quantified. Dimensionality reduction using t-distributed stochastic neighbor embedding (t-SNE) was applied to multiparametric flow cytometry data for immune profiling. In addition, publicly available transcriptomic datasets (GSE122091 and GSE46019) were analyzed to identify differentially expressed genes (DEGs) in IFN-γ- and TGF-β1-licensed MSCs, providing insight into potential molecular drivers of EV-mediated immunoregulation.
resultsLicensed EVs significantly inhibited pro-inflammatory THP-1 macrophage activation and promoted an anti-inflammatory phenotype, with reduced secretion of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β), increased IL-10 production, and decreased nitric oxide (NO) levels.. Compared to EVs from non-licensed MSCs, licensed EVs induced a greater proportion of regulatory T cells and exhibited enhanced suppression of allogeneic T cell proliferation. t-SNE analysis revealed a distinct immunoregulatory signature induced by licensed EVs, characterized by the emergence of a non-proliferative lymphocyte subset with elevated co-expression of CD4, CD25, and FOXP3. Transcriptomic analysis further revealed seven overlapping DEGs between IFN-γ- and TGF-β1-licensed MSCs, including both upregulated (GPR68, LIMK2, LIPG) and downregulated (EFNA5, PRKG1, DCLK1, TRIM2) genes, several of which are functionally implicated in EV-mediated immune regulation.
conclusionsSmall EVs derived from IFN-γ and TGF-β1-licensed MSCs exhibit demonstrate dose-dependent immunomodulatory trends in vitro, with enhanced effects observed at higher concentrations.. These findings suggest their potential utility in modulating both innate and adaptive immune responses, warranting further investigation for their application as a cell-free therapeutic strategy in immune-mediated conditions.
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