ArticleCell communication and signaling : CCS2024
Endothelial cell-derived extracellular vesicles modulate the therapeutic efficacy of mesenchymal stem cells through IDH2/TET pathway in ARDS.
Article in Cell communication and signaling : CCS, 2024. 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.
- The landscape of protein post-translational modifications in the pathogenesis of acute respiratory distress syndrome.Journal of thoracic disease · 2026Review
- Cryogenic Electron Microscopy of Extracellular Vesicles from Temozolomide-Treated Glioblastoma Cells Reveals Great Morphological Heterogeneity.Nanomaterials (Basel, Switzerland) · 2026Article
- Reproductive and Developmental Toxicity of Human Umbilical Cord Blood Mononuclear Cells.Biomedicines · 2026Article
- The metabolite α-ketoglutarate induces AIM2-dependent PANoptosis through demethylase TET2.Cell communication and signaling : CCS · 2026Article
- Endothelium-Treg Communication Through Extracellular Vesicle Transfer Exacerbates Acute Respiratory Distress Syndrome.Journal of extracellular vesicles · 2026Article
- Pulmonary Vascular Endothelial Cells in Lung Diseases: Mechanisms, Therapeutic Strategies, and Future Directions.Cell proliferation · 2026Review
- Therapeutic potential of stem cell-derived extracellular vesicles in aging and regeneration.Frontiers in aging · 2026Review
- Beyond immunomodulation: mechanisms and synergistic strategies of mesenchymal stem cells in promoting alveolar epithelial and endothelial repair in ARDS.Frontiers in immunology · 2026Review
- MSCs and MSC-Exos in pediatric ARDS treatment: translational research and the reshaping of nursing roles.Frontiers in pediatrics · 2026Review
- The Extracellular Matrix and the Immune System in Acute Lung Injury: Partners in Damage and Repair.Biomedicines · 2025Review
- Extracellular vesicles in metabolic perspective: mechanism and targeted therapy.Journal of nanobiotechnology · 2025Review
- Application of nanoparticles in the treatment of acute lung injury: Current situation and future directions.Materials today. Bio · 2025Review
- Immunomodulatory effects and clinical application of exosomes derived from mesenchymal stem cells.World journal of stem cells · 2025Review
- Blood-Derived Extracellular Vesicles as a Promising Liquid Biopsy Diagnostic Tool for Early Cancer Detection.Biomolecules · 2024Review
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13 authors.
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Abstract
backgroundAcute respiratory distress syndrome (ARDS) is a severe and fatal disease. Although mesenchymal stem cell (MSC)-based therapy has shown remarkable efficacy in treating ARDS in animal experiments, clinical outcomes have been unsatisfactory, which may be attributed to the influence of the lung microenvironment during MSC administration. Extracellular vesicles (EVs) derived from endothelial cells (EC-EVs) are important components of the lung microenvironment and play a crucial role in ARDS. However, the effect of EC-EVs on MSC therapy is still unclear. In this study, we established lipopolysaccharide (LPS) - induced acute lung injury model to evaluate the impact of EC-EVs on the reparative effects of bone marrow-derived MSC (BM-MSC) transplantation on lung injury and to unravel the underlying mechanisms.
methodsEVs were isolated from bronchoalveolar lavage fluid of mice with LPS - induced acute lung injury and patients with ARDS using ultracentrifugation. and the changes of EC-EVs were analysed using nanoflow cytometry analysis. In vitro assays were performed to establish the impact of EC-EVs on MSC functions, including cell viability and migration, while in vivo studies were performed to validate the therapeutic effect of EC-EVs on MSCs. RNA-Seq analysis, small interfering RNA (siRNA), and a recombinant lentivirus were used to investigate the underlying mechanisms.
resultsCompared with that in non-ARDS patients, the quantity of EC-EVs in the lung microenvironment was significantly greater in patients with ARDS. EVs derived from lipopolysaccharide-stimulated endothelial cells (LPS-EVs) significantly decreased the viability and migration of BM-MSCs. Furthermore, engrafting BM-MSCs pretreated with LPS-EVs promoted the release of inflammatory cytokines and increased pulmonary microvascular permeability, aggravating lung injury. Mechanistically, LPS-EVs reduced the expression level of isocitrate dehydrogenase 2 (IDH2), which catalyses the formation of α-ketoglutarate (α-KG), an intermediate product of the tricarboxylic acid (TCA) cycle, in BM-MSCs. α-KG is a cofactor for ten-eleven translocation (TET) enzymes, which catalyse DNA hydroxymethylation in BM-MSCs.
conclusionsThis study revealed that EC-EVs in the lung microenvironment during ARDS can affect the therapeutic efficacy of BM-MSCs through the IDH2/TET pathway, providing potential strategies for improving the therapeutic efficacy of MSC-based therapy in the clinic.
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