ArticleJournal of nanobiotechnology2021
Extracellular vesicles derived from hypoxia-preconditioned olfactory mucosa mesenchymal stem cells enhance angiogenesis via miR-612.
Article in Journal of nanobiotechnology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers, 1 of them a synthesis that pooled it.
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Who cites it
91 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Therapeutic potential of stem cell extracellular vesicles for ischemic stroke in preclinical rodent models: a meta-analysis.Stem cell research & therapy · 2023Pooled it
- From pathogenic to reparative: Context-Dependent function of extracellular vesicles in osteoarthritis.Bioactive materials · 2027Review
- The Biological Basis, Mechanisms of Action, and Optimization Strategies of Exosomes Derived from Mesenchymal Stem Cells for the Treatment of Alzheimer's Disease.Molecular neurobiology · 2026Review
- Advancing MSC-EV Therapies: Harnessing Preconditioning and Mito-EVs to Tackle Neuroinflammation and Neurodegeneration.Pharmaceutics · 2026Review
- Exploring Biomarkers and Regulatory Mechanisms Associated with Lytic Cell Death in Allergic Rhinitis Based on Transcriptome Analysis.Biomedicines · 2026Article
- Cargo-driven extracellular vesicles as pharmaceutical nanocarriers: A pharmaceutics-oriented comparison of animal exosomes and plant-derived exosome-like nanoparticles.International journal of pharmaceutics: X · 2026Review
- Biorthogonal click-immobilized probiotic membrane vesicles in a dynamic hydrogel for accelerated and scar-minimized wound healing.Materials today. Bio · 2026Article
- Review
- Engineering Approaches to Modify Immunomodulatory Functions of Mesenchymal Stromal Cells (MSCs): Tissue Regeneration and Clinical Application.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Human umbilical cord-derived mesenchymal stem cell exosomes ameliorate hepatocyte ferroptosis and sepsis-associated liver injury by restoring iron homeostasis in hepatocytes.Journal of nanobiotechnology · 2026Article
- The Potential of Neural Stem Cell-derived Exosomes for the Treatment of Ischemic Stroke.Stem cell reviews and reports · 2026Review
- Dawn of a new era in olfactory regeneration: Pediatric stem cell therapy enters the era of long-term validation.World journal of stem cells · 2026Article
- Hypoxia-conditioned BMSC exosomes improve short-term spinal cord injury outcomes via the miR-615-3p/PDE4C-mediated cAMP/PKA pathway.Stem cell research & therapy · 2026Article
- Priming strategies to enhance the therapeutic efficacy of mesenchymal stromal/stem cell-derived vesicles in regenerative medicine.Extracellular vesicles and circulating nucleic acids · 2026Review
- Engineered MSC-Exosomes Delivering miRNAs for Respiratory Disease Diagnostics and Therapy: Opportunities and Challenges.International journal of nanomedicine · 2026Review
- Human umbilical cord mesenchymal stem cell-derived nanovesicles ameliorate acute lung injury by hsa-let-7g-5p inhibition of NF-κB/NLRP3 pathway.Extracellular vesicles and circulating nucleic acids · 2026Article
- Mesenchymal stem cells-derived extracellular vesicles as a novel drug delivery carrier: engineering strategies and clinical safety estimation.Frontiers in molecular biosciences · 2026Review
- PGC-1α mediates hypoxia-preconditioned olfactory mucosa mesenchymal stem cells improved neuroinflammatory response via inhibiting microglial ferroptosis in ischemic stroke.Journal of translational medicine · 2025Article
- Advanced nanotherapies for precision treatment of inflammatory lung diseases.Bioactive materials · 2025Review
- Article
31 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors.
Funding
Abstract
Mesenchymal stem cells (MSCs) play important roles in tissue repair and regeneration, such as the induction of angiogenesis, particularly under hypoxic conditions. However, the molecular mechanisms underlying hypoxic MSC activation remain largely unknown. MSC-derived extracellular vesicles (EVs) are vital mediators of cell-to-cell communication and can be directly utilized as therapeutic agents for tissue repair and regeneration. Here, we explored the effects of EVs from human hypoxic olfactory mucosa MSCs (OM-MSCs) on angiogenesis and its underlying mechanism. EVs were isolated from normoxic (N) OM-MSCs (N-EVs) and hypoxic (H) OM-MSCs (H-EVs) using differential centrifugation and identified by transmission electron microscopy and flow cytometry. In vitro and in vivo, both types of OM-MSC-EVs promoted the proliferation, migration, and angiogenic activities of human brain microvascular endothelial cells (HBMECs). In addition, angiogenesis-stimulatory activity in the H-EV group was significantly enhanced compared to the N-EV group. MicroRNA profiling revealed a higher abundance of miR-612 in H-EVs than in N-EVs, while miR-612 inactivation abolished the N-EV treatment benefit. To explore the roles of miR-612, overexpression and knock-down experiments were performed using a mimic and inhibitor or agomir and antagomir of miR-612. The miR-612 target genes were confirmed using the luciferase reporter assay. Gain- and loss-of-function studies allowed the validation of miR-612 (enriched in hypoxic OM-MSC-EVs) as a functional messenger that stimulates angiogenesis and represses the expression of TP53 by targeting its 3'-untranslated region. Further functional assays showed that hypoxic OM-MSC-EVs promote paracrine Hypoxia-inducible factor 1-alpha (HIF-1α)-Vascular endothelial growth factor (VEGF) signaling in HBMECs via the exosomal miR-612-TP53-HIF-1α-VEGF axis. These findings suggest that hypoxic OM-MSC-EVs may represent a promising strategy for ischemic disease by promoting angiogenesis via miR-612 transfer.
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