ArticleBMC medicine2023
Hypoxia enhances anti-fibrotic properties of extracellular vesicles derived from hiPSCs via the miR302b-3p/TGFβ/SMAD2 axis.
Article in BMC medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 40 citations in OpenAlex.
- Effects Of Oxygen Tension On iPSC Morphology And Small Extracellular Vesicle Particle Characteristics.Stem cell reviews and reports · 2026Article
- Small Extracellular Vesicles in Cardioprotection, Cardiac Repair, and Regeneration: Cargo Mechanisms, Producer Cell Sources, and Translational Development.Biomedicines · 2026Review
- Cardiac regeneration and repair: the emerging mechanisms and therapeutic approaches.Molecular biomedicine · 2026Review
- Stem Cells and Their Derivatives in Cardiac Fibrosis Therapy: Challenges and Perspectives.Cells · 2026Review
- Source-Specific Extracellular Vesicle Functions and Engineering Strategies for Chronic Pain Management: A Comprehensive Review.International journal of nanomedicine · 2026Review
- Recent advances in biomarkers for cardiac fibrosis.Frontiers in cardiovascular medicine · 2026Review
- Platelet-bioengineered hiPSC-sEVs achieve targeted repair of fibrotic sinoatrial node in preclinical SND models.Nature communications · 2025Article
- Role of Anti-Inflammatory and Antioxidant Properties of Natural Products in Curing Cardiovascular Diseases.Current issues in molecular biology · 2025Review
- Fibroblasts: A Molecular and Pathophysiological Perspective.Biomedicines · 2025Article
- Hormonal Atrial Fibrillation: Pathophysiological Mechanisms That Trigger and Sustain the Arrhythmic Circuits.Biomedicines · 2025Review
- Cardiac repair and regeneration: cell therapy, in vivo reprogramming, and the promise of extracellular vesicles.Experimental & molecular medicine · 2025Review
- Hypoxia and Tissue Regeneration: Adaptive Mechanisms and Therapeutic Opportunities.International journal of molecular sciences · 2025Review
- Atrial Fibrillation in Diabetes: Pathogenesis and Targeted Rhythm Control Strategies.Current issues in molecular biology · 2025Review
- Hypoxic Neural Stem Cells Enhance Spinal Cord Repair Through HIF-1a/RAB17-Driven Extracellular Vesicle Release.Journal of extracellular vesicles · 2025Article
- Translation of pathophysiological mechanisms of atrial fibrosis into new diagnostic and therapeutic approaches.Nature reviews. Cardiology · 2025Review
- Extracellular vesicle therapeutics for cardiac repair.Journal of molecular and cellular cardiology · 2025Review
- Innovative Therapeutic Strategies for Myocardial Infarction Across Various Stages: Non-Coding RNA and Stem Cells.International journal of molecular sciences · 2024Review
- Atrial Fibrosis in Atrial Fibrillation: Mechanistic Insights, Diagnostic Challenges, and Emerging Therapeutic Targets.International journal of molecular sciences · 2024Review
- Hypoxic extracellular vesicles from hiPSCs protect cardiomyocytes from oxidative damage by transferring antioxidant proteins and enhancing Akt/Erk/NRF2 signaling.Cell communication and signaling : CCS · 2024Article
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCardiac fibrosis is one of the top killers among fibrotic diseases and continues to be a global unaddressed health problem. The lack of effective treatment combined with the considerable socioeconomic burden highlights the urgent need for innovative therapeutic options. Here, we evaluated the anti-fibrotic properties of extracellular vesicles (EVs) derived from human induced pluripotent stem cells (hiPSCs) that were cultured under various oxygen concentrations.
methodsEVs were isolated from three hiPSC lines cultured under normoxia (21% O
resultsWe provide evidence that an oxygen concentration of 5% enhances the anti-fibrotic effects of hiPS-EVs. These EVs were more effective in reducing pro-fibrotic markers in activated human cardiac fibroblasts, when compared to EV-N or EV-H3. We show that EV-H5 act through the canonical TGFβ/SMAD pathway, primarily via miR-302b-3p, which is the most abundant miRNA in EV-H5. Our results show that EV-H5 not only target transcripts of several profibrotic genes, including SMAD2 and TGFBR2, but also reduce the stiffness of activated fibroblasts. In a mouse model of heart fibrosis, EV-H5 outperformed EV-N in suppressing the inflammatory response in the host and by attenuating collagen deposition and reducing pro-fibrotic markers in cardiac tissue.
conclusionsIn this work, we provide evidence of superior anti-fibrotic properties of EV-H5 over EV-N or EV-H3. Our study uncovers that fine regulation of oxygen concentration in the cellular environment may enhance the anti-fibrotic effects of hiPS-EVs, which has great potential to be applied for heart regeneration.
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