The Role of Small Extracellular Vesicles Derived from Glial Cells in the Central Nervous System under both Normal and Pathological Conditions

Neurochemical Research, Год журнала: 2025, Номер 50(2)

Опубликована: Янв. 30, 2025

Язык: Английский

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Hepatocyte‐derived exosomes deliver the lncRNA CYTOR to hepatic stellate cells and promote liver fibrosis

Journal of Cellular and Molecular Medicine, Год журнала: 2024, Номер 28(8)

Опубликована: Март 23, 2024

Abstract Liver fibrosis is characterized by the activation and transformation of hepatic stellate cells (HSCs) induced various injury factors. The degree liver can be significantly improved, but persistent factors present a significant therapeutic challenge. Hepatocytes are most important parenchymal cell type in liver. In this study, we explored molecular mechanisms which damaged activate HSCs through extracellular vesicles. We established coculture model LO2 LX2 validated its exosomal transmission activity. Subsequently, differentially expressed long noncoding RNAs (lncRNAs) were screened RNA sequencing their action as competing endogenous (ceRNAs) further confirmed using biological methods, such FISH luciferase assays. Damaged upregulation fibrosis‐related markers. Exosomes extracted identified from supernatant fraction contained lncRNA cytoskeleton regulator (CYTOR) that competed with microRNA‐125 (miR‐125) for binding to glial line‐derived neurotrophic factor (GDNF) HSCs, turn, promoting activation. MiR‐125 could target regulate both CYTOR GDNF vice versa, verified assay. an vivo model, vesicles formation fibrosis. Notably, downregulation within effectively inhibited exosomes upregulated modulates expression downstream activity ceRNA, providing effective mechanism HSCs.

Язык: Английский

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Delivery-mediated exosomal therapeutics in ischemia–reperfusion injury: advances, mechanisms, and future directions

Nano Convergence, Год журнала: 2024, Номер 11(1)

Опубликована: Апрель 30, 2024

Ischemia-reperfusion injury (IRI) poses significant challenges across various organ systems, including the heart, brain, and kidneys. Exosomes have shown great potentials applications in mitigating IRI-induced cell tissue damage through modulating inflammatory responses, enhancing angiogenesis, promoting repair. Despite these advances, a more systematic understanding of exosomes from different sources their biotransport is critical for optimizing therapeutic efficacy accelerating clinical adoption IRI therapies. Therefore, this review article overviews administration routes sources, such as mesenchymal stem cells other somatic cells, context treatment. Furthermore, covers how delivered modulate molecular pathways recipient aiding prevention death promotions regeneration models. In end, discusses ongoing research efforts propose future directions exosome-based

Язык: Английский

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Metabolic reprogramming and astrocytes polarization following ischemic stroke

Free Radical Biology and Medicine, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

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Stem Cell-Derived Extracellular Vesicle-Mediated Therapeutic Signaling in Spinal Cord Injury

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(2), С. 723 - 723

Опубликована: Янв. 16, 2025

Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have emerged as a promising therapeutic strategy for spinal cord injury (SCI). These nanosized possess unique properties such low immunogenicity and the ability to cross biological barriers, making them ideal carriers delivering bioactive molecules injured tissues. MSC-EVs been demonstrated exert multiple beneficial effects in SCI, including reducing inflammation, promoting neuroprotection, enhancing axonal regeneration. Recent studies delved into molecular mechanisms underlying MSC-EV-mediated effects. Exosomal microRNAs (miRNAs) identified key regulators of various cellular processes involved SCI pathogenesis repair. miRNAs can influence oxidative stress, apoptosis by modulating gene expression. This review summarized current state MSC-EV-based therapies highlighting potential clinical applications. We discussed challenges limitations translating these practice, inconsistent EV production, complex cargo composition, need targeted delivery strategies. Future research should focus on optimizing production characterization, identifying miRNAs, developing innovative systems maximize SCI.

Язык: Английский

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Targeting astrocytes polarization after spinal cord injury: a promising direction

Frontiers in Cellular Neuroscience, Год журнала: 2024, Номер 18

Опубликована: Окт. 16, 2024

Spinal cord injury (SCI) is a serious neurological that causes severe trauma to motor and sensory functions. Although long considered incurable, recent research has brought new hope for functional recovery from SCI. After SCI, astrocytes are activated into many polarization states. Here we discuss the two most important classical phenotypes: ‘A1’ neurotoxic phenotype ‘A2’ neuroprotective phenotype, with A1 being impeding neurorecovery, A2 neuroprotective. This paper discusses changes in astrocyte responsiveness after SCI pros cons of their It also elucidates feasibility as therapeutic target neuroprotection. In future, multiple intervention strategies targeting expected gain wider clinical application, ultimately improving motor-sensory function quality life patients.

Язык: Английский

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The Yin and Yang of Microglia-Derived Extracellular Vesicles in CNS Injury and Diseases

Cells, Год журнала: 2024, Номер 13(22), С. 1834 - 1834

Опубликована: Ноя. 6, 2024

Microglia, the resident immune cells of central nervous system (CNS), play a crucial role in maintaining neural homeostasis but can also contribute to disease and injury when this state is disrupted or conversely pivotal neurorepair. One way that microglia exert their effects through secretion small vesicles, microglia-derived exosomes (MGEVs). Exosomes facilitate intercellular communication transported cargoes proteins, lipids, RNA, other bioactive molecules alter behavior internalize them. Under normal physiological conditions, MGEVs are essential homeostasis, whereas dysregulation production and/or alterations have been implicated pathogenesis numerous neurodegenerative diseases, including Alzheimer's (AD), Parkinson's (PD), multiple sclerosis (MS), spinal cord (SCI), traumatic brain (TBI). In contrast, may offer therapeutic potential by reversing inflammation being amenable engineering for delivery beneficial biologics drugs. The determined phenotypic parent microglia. from anti-inflammatory pro-regenerative support neurorepair cell survival delivering neurotrophic factors, mediators, molecular chaperones. Further, deliver components like mitochondrial DNA (mtDNA) proteins damaged neurons enhance cellular metabolism resilience. derived pro-inflammatory detrimental on health. Their cargo often contains cytokines, involved oxidative stress, neurotoxic which exacerbate neuroinflammation, neuronal damage, impair synaptic function, hindering processes. neurodegeneration injury-whether harmful-largely depends how they modulate pro- factors cargo, cytokines microRNAs. addition, propagation pathological such as amyloid-beta alpha-synuclein, progression disorders AD PD, transfer apoptotic necrotic induce neuron toxicity trigger glial scarring during neurological injury. review, we provided comprehensive up-to-date understanding mechanisms underlying multifaceted disease. particular, specific exosome various either recovery, will be discussed. has highlighted methodologies employed cell-selective targeting. Understanding influence balance between signaling CNS developing new strategies diseases neurotrauma.

Язык: Английский

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Engineered Extracellular Vesicles Modified by Angiopep-2 Peptide Promote Targeted Repair of Spinal Cord Injury and Brain Inflammation

ACS Nano, Год журнала: 2025, Номер unknown

Опубликована: Янв. 24, 2025

Engineered extracellular vesicles play an increasingly important role in the treatment of spinal cord injury. In order to prepare more effective engineered vesicles, we biologically modified M2 microglia. Angiopep-2 (Ang2) is oligopeptide that can target blood–brain barrier. Through single-cell sequencing and immunofluorescence experiments, confirmed expression LRP-1, targeted receptor Ang2, was elevated after Subsequently, integrated Ang2 peptide segment into microglia obtain Ang2-EVs, which could successfully site However, improve function pretreated with melatonin, has anti-inflammatory effects, M-Ang2-EVs. The results single-nucleus mouse verified neurons OPCs gradually transformed subtypes related nerve repair functions This consistent enrichment analysis miRNAs contained We further through experiments M-Ang2-EVs promote microglia/macrophages phagocytose sphingomyelin, axon remyelination elongation, maintain integrity blood-spinal Since also barrier, found reduce brain inflammation from Our study applied injury enhance targeting injured cells, construct brain.

Язык: Английский

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Pre-treated Mesenchymal Stem Cell-Derived Exosomes: A New Perspective for Accelerating Spinal Cord Injury Repair

European Journal of Pharmacology, Год журнала: 2025, Номер 992, С. 177349 - 177349

Опубликована: Фев. 5, 2025

Spinal cord injury (SCI) is a devastating event for the central nervous system (CNS), often resulting in loss of sensory and motor functions. It profoundly affects both physiological psychological well-being patients, reducing their quality life while also imposing significant economic pressure on families healthcare system. Due to complex pathophysiology SCI, effective treatments promoting recovery remain scarce. Mesenchymal stem cell-derived exosomes (MSC-Exos) offer advantages such as low immunogenicity, good biocompatibility, ability cross blood-spinal barrier (BSCB). In preclinical studies, they have progressively shown efficacy SCI repair functional recovery. However, yield insufficient targeting MSC-Exos limit therapeutic efficacy. Currently, genetic engineering other preprocessing techniques are being employed optimize properties exosomes, thereby enhancing potential. Therefore, this paper provides an overview biogenesis exosomes. summarizes current approaches optimizing exosome performance. Additionally, it details mechanisms through which optimized provide neuroprotection explores potential combined involving hydrogels.

Язык: Английский

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Vincristine Regulates C/EBP-β/TGF-β1 to Promote A1 Astrocyte Polarization and Induce Neuropathic Pain

Drug Design Development and Therapy, Год журнала: 2025, Номер Volume 19, С. 827 - 840

Опубликована: Фев. 1, 2025

Background: The neuropathic pain side induced by Vincristine severely limit its clinical application. However, the mechanism of is not clear. This study aims to clarify C/EBP-β regulating TGF-β 1 mediated spinal astrocyte A1/A2 polarization in caused vincristine. Methods: Neuropathic model was established rats intraperitoneal injection (VCR). In vitro experiment, constructed Vincristine, and si-C/EBP-β regulated before VCR administration. Pain threshold measured thermal withdrawal latency (TWL) mechanical (MWT), Elisa used detect expression level inflammatory factors, qRT PCR Western blotting were markers, C/EBP-β, 1, p-smad2 p-smad3. Results: Following administration, TWL MWT exhibited a decrease. Additionally, there an increase A1 astrocytes, while A2 remained relatively unchanged. Furthermore, levels pro-inflammatory factors elevated, whereas no significant alterations observed anti-inflammatory factors. Notably, promoted 1. inhibitor alleviated release proinflammatory ameliorated abnormal pain. Moreover, silencing reversed enhanced attenuated factor release. Conclusion: cord inflammation promoting astrocytes via upregulating C/EBP-β/TGF-β signal pathway, thus leading It different from traditional this shown new pathway for polarization, which may provide possibility treatment Keywords: pain, neuroinflammation

Язык: Английский

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