Human neural stem cell-derived exosomes activate PINK1/Parkin pathway to protect against oxidative stress-induced neuronal injury in ischemic stroke

Journal of Translational Medicine, Год журнала: 2025, Номер 23(1)

Опубликована: Апрель 5, 2025

Mitochondria play a critical role in oxidative stress (OS)-induced neuronal injury during ischemic stroke (IS), making them promising therapeutic targets. Mounting evidence underscores the extraordinary promise of exosomes derived from human neural stem cells (hNSCs) management central nervous system (CNS) diseases. Nonetheless, precise mechanisms by which these target mitochondria to ameliorate effects IS remain only partially elucidated. This study investigates protective hNSC (hNSC-Exos) on damage. Using rat model middle cerebral artery occlusion (MCAO) vivo and OS-induced HT22 vitro. Firstly, our research group independently isolated subsequently prepared hNSC-Exos. In vivo, MCAO rats were restored blood flow perfusion simulate ischemia-reperfusion injury, hNSC-Exos injected through stereotaxic injection into brain. Subsequently, evaluated, including histological studies, behavioral assessments. H2O2 was used OS environment MCAO, then its evaluated co-culturing with hNSC-Exos, immunofluorescence staining, western blotting (WB), quantitative real time PCR (qRT-PCR). process exploring specific mechanisms, we utilized RNA sequencing (RNA-seq) detect potential induction mitophagy cells. Afterwards, employed series mitochondrial function assessments autophagy related detection techniques, measuring membrane potential, reactive oxygen species (ROS) levels, transmission electron microscopy (TEM) imaging, monodansylcadaverine (MDC) mCherry-GFP-LC3B staining. addition, further investigated regulatory pathway using inhibitor mdivi-1 knocking out PTEN induced kinase 1 (PINK1) Administration significantly ameliorated brain tissue damage enhanced outcomes rats. treatment led reduction apoptosis facilitated normalization impaired neurogenesis neuroplasticity. Notably, application vitro resulted an upregulation cells, thereby remedying dysfunction. We demonstrate that activate via PINK1/Parkin pathway, improving reducing apoptosis. These findings suggest alleviate regulating pathway. reveals novel cell-derived therapy promoting neuroprotection their as approach for OS-associated CNS diseases, IS.

Язык: Английский

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Neuroprotective effect of small extracellular vesicle-mediated targeting of AMPKα2 in cerebral ischemia

Metabolism, Год журнала: 2025, Номер unknown, С. 156160 - 156160

Опубликована: Фев. 1, 2025

Язык: Английский

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Apelin-13/APJ promotes neural stem cells to repair ischemic stroke

Tissue and Cell, Год журнала: 2025, Номер 95, С. 102872 - 102872

Опубликована: Март 22, 2025

Neural stem cell therapy is considered as a promising new for ischemic stroke. However, the therapeutic efficacy of neural cells (NSCs) hampered by effects cerebral ischemia and hypoxia, resulting in suboptimal performance. Drug stimulation can further improve NSCs stroke, among which small molecule peptide Apelin-13 could have potential. In this study, we simulated anoxic microenvironment oxygen-glucose deprivation (OGD) to observe improvement on treatment-related functions. Six hours OGD treatment suppressed viability NSCs, while 100 nM mitigated suppression. Additionally, reduced migration capability but enhanced ability under conditions. also increased rate apoptotic decreased ratio Bcl-2 Bax. environment, BDNF expression was elevated, level. APJ endogenous receptor Apelin-13. We knocked down observed that effect abolished environment compared with negative control group knockdown, upregulation brain derived neurotrophic factor (BDNF) lost. Our study found enhances fosters migration, diminishes apoptosis, augments conditions through receptor. The Apelin-13/APJ system may play beneficial role activating purpose treating This positive be mediated downstream effector protein, BDNF.

Язык: Английский

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The Role of Exosomes Derived from Various Sources in Facilitating the Healing of Chronic Refractory Wounds

Pharmacological Research, Год журнала: 2025, Номер unknown, С. 107753 - 107753

Опубликована: Апрель 1, 2025

Chronic refractory wounds (CRWs) represent a common and challenging issue in clinical practice, including diabetic foot ulcers, pressure venous arterial ulcers. These significantly impact patients' quality of life may lead to severe consequences such as amputation. Their treatment requires comprehensive consideration both the patient's overall physical condition local wound situation. The major challenges include complex pathogenesis, long cycle, high recurrence rate, heavy economic on patients. Exosomes an emerging therapeutic modality with characteristics low immunogenicity, good biostability, targeting efficiency diseases. derived from different sources exhibit heterogeneity, demonstrating their respective advantages unique properties treatment. This article delves into potential applications mechanisms action exosomes various CRWs, aiming provide new perspectives ideas for management wounds.

Язык: Английский

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Therapeutic potential of microglia-derived extracellular vesicles in ischemic stroke

International Immunopharmacology, Год журнала: 2024, Номер 139, С. 112712 - 112712

Опубликована: Июль 19, 2024

Язык: Английский

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