Comparative study of extracellular vesicles derived from mesenchymal stem cells and brain endothelial cells attenuating blood–brain barrier permeability via regulating Caveolin-1-dependent ZO-1 and Claudin-5 endocytosis in acute ischemic stroke

Journal of Nanobiotechnology, Journal Year: 2023, Volume and Issue: 21(1)

Published: Feb. 28, 2023

Blood-brain barrier (BBB) disruption is a major adverse event after ischemic stroke (IS). Caveolin-1 (Cav-1), scaffolding protein, played multiple roles in BBB permeability IS, while the pros and cons of Cav-1 on remain controversial. Numerous studies revealed that extracellular vesicles (EVs), especially stem cells derived EVs, exerted therapeutic efficacy IS; however, mechanisms needed to be clearly illustrated. Herein, we compared protective integrity between bone marrow mesenchymal (BMSC-EVs) EVs from brain endothelial (BEC-EVs) acute IS investigated whether mechanism was associated with antagonizing Cav-1-dependent tight junction proteins endocytosis.BMSC-EVs BEC-EVs were isolated characterized by nanoparticle tracking analysis, western blotting, transmission electron microscope. Oxygen glucose deprivation (OGD) treated b. End3 utilized evaluate cell leakage. CCK-8 TRITC-dextran leakage assays used measure viability transwell monolayer permeability. Permanent middle cerebral artery occlusion (pMCAo) model established, intravenously administered rats. Animal neurological function tests applied, microvessels cortex. analyzed Evans Blue (EB) staining respectively. Co-IP assay siRNA/pcDNA 3.1 vector transfection employed verify endocytosis proteins.Both kinds similar efficacies reducing infarction volume enhancing expressions ZO-1 Claudin-5 24 h pMCAo At same time, BMSC-EVs outstanding ameliorating function. Simultaneously, both treatments suppressed highly expressed OGD-exposed microvessels, this more prominent administration. knockdown reduced OGD-treated recovered expressions, whereas overexpression aggravated enhanced colocalization Claudin-5. Furthermore, partly reversed lower administrations cells.Our results demonstrated stroke, antagonistic endocytosis. treatment superior suppression amelioration.

Language: Английский

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Neural Stem Cells Therapy for Ischemic Stroke: Progress and Challenges

Translational Stroke Research, Journal Year: 2022, Volume and Issue: 13(5), P. 665 - 675

Published: Jan. 15, 2022

Language: Английский

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Extracellular Vesicles Maintain Blood-Brain Barrier Integrity by the Suppression of Caveolin-1/CD147/VEGFR2/MMP Pathway After Ischemic Stroke

International Journal of Nanomedicine, Journal Year: 2024, Volume and Issue: Volume 19, P. 1451 - 1467

Published: Feb. 1, 2024

Background: Ischemic stroke (IS) causes tragic death and disability worldwide. However, effective therapeutic interventions are finite. After IS, blood–brain barrier (BBB) integrity is disrupted, resulting in deteriorating neurological function. As a novel therapeutic, extracellular vesicles (EVs) have shown ideal restorative effects on BBB post-stroke; however, the definite mechanisms remain ambiguous. In present study, we investigated curative of EVs derived from bone marrow mesenchymal stem cells brain endothelial (BMSC-EVs BEC-EVs) after acute IS. Methods: were isolated BMSCs BECs, effect vitro oxygen-glucose deprivation (OGD) insulted BECs model vivo rat middle cerebral artery occlusion (MCAo) model. The cell monolayer leakage, tight junction expression, metalloproteinase (MMP) activity evaluated, infarct volume function also analyzed. Results: administration two kinds not only enhanced ZO-1 Occludin expressions but reduced permeability MMP-2/9 OGD-insulted BECs. amelioration infarction, deficits, increasing levels, as well MMP inhibition was observed MCAo rats. Additionally, increased levels Caveolin-1, CD147, vascular growth factor receptor 2 (VEGFR2), A (VEGFA) microvessels downregulated treatment. vitro, employment Caveolin-1 CD147 siRNA partly suppressed VEGFR2, VEGFA leakage OGD expressions. Conclusion: Our study firstly demonstrates that BEC BMSC-EVs administrations maintain via suppression Caveolin-1/CD147/VEGFR2/MMP pathway efficacy superior to BEC-EVs. Keywords: vesicles, ischemic stroke, matrix metalloproteinase, blood-brain

Language: Английский

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Revolutionizing Ischemic Stroke Diagnosis and Treatment: The Promising Role of Neurovascular Unit-Derived Extracellular Vesicles

Biomolecules, Journal Year: 2024, Volume and Issue: 14(3), P. 378 - 378

Published: March 20, 2024

Ischemic stroke is a fatal and disabling disease worldwide imposes significant burden on society. At present, biological markers that can be conveniently measured in body fluids are lacking for the diagnosis of ischemic stroke, there no effective treatment methods to improve neurological function after stroke. Therefore, new ways diagnosing treating urgently needed. The neurovascular unit, composed neurons, astrocytes, microglia, other components, plays crucial role onset progression Extracellular vesicles nanoscale lipid bilayer secreted by various cells. key extracellular vesicles, which released cells unit serve as facilitators cellular communication, has been extensively documented recent literature. Here, we highlight unit-derived current status vesicle engineering treatment, problems encountered clinical translation therapies. derived from could provide an important contribution diagnostic therapeutic tools future, more studies this area should carried out.

Language: Английский

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Both extracellular vesicles from helicobacter pylori-infected cells and helicobacter pylori outer membrane vesicles are involved in gastric/extragastric diseases

European journal of medical research, Journal Year: 2023, Volume and Issue: 28(1)

Published: Nov. 6, 2023

Abstract Bacterial-derived extracellular vesicles (EVs) have emerged as crucial mediators in the cross-talk between hosts and pathogens, playing a significant role infectious diseases cancers. Among these Helicobacter pylori ( H. ) is particularly important bacterium implicated various gastrointestinal disorders, gastric cancers, systemic illnesses. achieves effects by stimulating host cells to secrete EVs generating internal outer membrane (OMVs). The derived from -infected modulate inflammatory signaling pathways, thereby affecting cell proliferation, apoptosis, cytokine release, immune modification, endothelial dysfunction, well disrupting cellular junctional structures inducing cytoskeletal reorganization. In addition, OMVs isolated play pivotal shaping subsequent immunopathological responses. These incite both immunosuppressive reactions within environment, facilitating pathogen evasion of defenses invasion cells. Despite this growing understanding, research involving -derived remains its early stages across different domains. comprehensive review, we present recent advancements elucidating contributions EV components, such non-coding RNAs (ncRNAs) proteins, pathogenesis extragastric diseases. Furthermore, highlight their potential utility biomarkers, therapeutic targets, vehicles for targeted delivery.

Language: Английский

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Exosomes: The endogenous nanomaterials packed with potential for diagnosis and treatment of neurologic disorders

Colloids and Surfaces B Biointerfaces, Journal Year: 2024, Volume and Issue: 239, P. 113938 - 113938

Published: May 3, 2024

Language: Английский

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Extracellular Vesicles as a Potential Therapy for Stroke

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 3130 - 3130

Published: March 28, 2025

Although thrombolytic therapy has enjoyed relative success, limitations remain, such as a narrow therapeutic window and inconsistent efficacy. Consequently, there is pressing need to develop novel approaches. In recent years, extracellular vesicles (EVs) have garnered increasing attention potential alternative stem cell therapy. Because of their ability cross the blood-brain barrier exert neuroprotective effects in cerebral ischemia hemorrhage, exploration EVs for clinical application stroke treatment expanding. are characterized by high heterogeneity, with composition closely mirroring that parent cells. This property enables distinguish between thus facilitating more rapid accurate diagnosis. Additionally, can be engineered carry specific molecules, miRNAs, targeting them cells, potentially enhancing outcome improving prognosis. this review, we will also explore methodologies isolation extraction EVs, critically evaluating advantages disadvantages various commonly employed separation techniques. Furthermore, briefly address current EV preservation administration methods, providing comprehensive overview state EV-based therapies treatment.

Language: Английский

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Preserving Blood–Brain Barrier Integrity in Ischemic Stroke: a Review on MSCs-sEVs Content and Potential Molecular Targets

Molecular Neurobiology, Journal Year: 2025, Volume and Issue: unknown

Published: April 21, 2025

Language: Английский

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Therapeutic management of ischemic stroke

Naunyn-Schmiedeberg s Archives of Pharmacology, Journal Year: 2023, Volume and Issue: 397(5), P. 2651 - 2679

Published: Nov. 15, 2023

Language: Английский

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Stem Cell-derived Extracellular Vesicles: A Promising Nano Delivery Platform to the Brain?

Stem Cell Reviews and Reports, Journal Year: 2022, Volume and Issue: 19(2), P. 285 - 308

Published: Sept. 29, 2022

Language: Английский

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