ArticleInternational journal of nanomedicine2024
Nebulization of Hypoxic hUCMSC-EVs Attenuates Airway Epithelial Barrier Defects in Chronic Asthma Mice by Transferring CAV-1.
Article in International journal of nanomedicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Emerging therapeutic potential of umbilical cord-derived extracellular vesicles in lung-injurious diseases: a review of recent advances.Stem cell research & therapy · 2026Review
- Decoding lung-kidney interactions in sepsis: an integrated view of molecular mechanisms, pathophysiology, and therapeutic interventions.Frontiers in immunology · 2026Review
- Inhalable extracellular vesicles as cell-free therapeutics for chronic respiratory disease.Frontiers in bioengineering and biotechnology · 2026Review
- Engineered hUCMSC-derived extracellular vesicles deliver circ-0000258 to restore p53-mediated tumor suppression in papillary thyroid carcinoma.BMC cancer · 2025Article
- Extracellular Vesicles: Multimodal Tools for Diagnosis, Prognosis, and Therapy in Respiratory Diseases.Expert reviews in molecular medicine · 2025Review
- ROS-responsive 3D biological scaffold delivers hypoxia-primed extracellular vesicles for targeted modulation of neuroinflammation in intracerebral hemorrhage.Stem cell research & therapy · 2025Article
- Nebulized inhalation of extracellular vesicles containing SPOCK2 suppresses lung adenocarcinoma progression via MAPK inhibition.Discover oncology · 2025Article
- Review
- Asthma and stem cell therapy.World journal of stem cells · 2025Review
- Biological Nanotherapeutics Derived From Human Umbilical Cord Mesenchymal Stem Cells: Mechanisms and Translational Potential in Multisystem Therapies for Regeneration and Oncology.International journal of nanomedicine · 2025Review
- Effect Analysis of Extracellular Vesicles in the Treatment of Bronchopulmonary Dysplasia via Different Drug Delivery and Administration Routes.International journal of nanomedicine · 2025Review
- Therapeutic Efficacy and Promise of Human Umbilical Cord Mesenchymal Stem Cell-Derived Extracellular Vesicles in Aging and Age-Related Disorders.International journal of molecular sciences · 2024Review
- Research advances of extracellular vesicles in lung diseases.Cell transplantationReview
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Authors and funding
9 authors.
Funding
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Abstract
Background: Nebulization of hypoxic human umbilical cord mesenchymal stem cell-derived extracellular vesicles (Hypo-EVs) can suppress airway inflammation and remodeling in a chronic asthmatic mouse; however, the exact mechanism remains unclear. Recently, airway epithelial barrier defects have been regarded as crucial therapeutic targets in asthma. The aim of this study was to investigate whether and how Hypo-EVs protect against the disruption of the airway epithelial barrier under asthmatic conditions. Methods: The therapeutic effects of Hypo-EVs on airway epithelial barrier defects were evaluated in ovalbumin (OVA)-induced asthmatic mice and in IL-4 and IL-13-induced HBE135-E6E7 cell models by detecting cell monolayer leakage and junctional protein expression. The protein levels in Hypo-EVs were determined by Western blotting, and a gene knockdown approach was used to investigate the biofactors in Hypo-EVs. Results: Nebulization of Hypo-EVs directly alleviated airway epithelial barrier defects in asthmatic mice, as evidenced by colocalization with bronchial epithelial cells, decreased albumin concentration, and increased ZO-1 and E-cadherin expression. In vitro, Hypo-EV treatment dramatically rescued the increase in airway cell permeability, and upregulated the ZO-1 and E-cadherin protein expressions. Based on WB analysis, we found that caveolin-1 (CAV-1) was strongly enriched in Hypo-EVs. The knockdown of CAV-1 protein levels in Hypo-EVs significantly impaired Hypo-EV-mediated barrier protection in vitro and in vivo. Moreover, CAV-1 knockdown significantly abolished the beneficial effects of Hypo-EVs on airway inflammation and remodeling in asthmatic mice. In addition, we showed that IL-4/IL-13-induced airway epithelial barrier defects were mainly related to activation of STAT6 phosphorylation (p-STAT6), and overexpression of CAV-1 or Hypo-EV treatment inhibited the levels of p-STAT6 in IL-4/IL-13-induced HBE135-E6E7 cells. Conclusion: Nebulization of Hypo-EVs can attenuate airway epithelial barrier defects in asthma by delivering CAV-1 to inhibit p-STAT6 expression and may be used to treat other barrier defect diseases.
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