Combination of EPC-EXs and NPC-EXs with miR-126 and miR-210 overexpression produces better therapeutic effects on ischemic stroke by protecting neurons through the Nox2/ROS and BDNF/TrkB pathways

Xu, Xiaobing; Zhang, Huiting; Li, Jiahui; Chen, Yanyu; Zhong, Wangtao; Chen, Yanfang; Ma, Xiaotang

doi:10.1016/j.expneurol.2022.114235

Cited by 20 publications

(12 citation statements)

References 82 publications

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“…As shown in Fig. 1 and 28 studies [ 17 , 21 – 47 ] ultimately met our criteria and were included in this review. Details of these studies are presented in Table 1 .…”

Section: Resultsmentioning

confidence: 99%

“…For example, stem cell-derived EVs have been shown to up-regulate the expression of genes of multiple angiogenesis pathways such as vascular endothelial growth factor (VEGF), angiopoietin 1 (ANG1), angiopoietin 2 (ANG2), matrix metallopeptidase 9 (MMP9), thrombopoietin 1 (TSP1), so as to promote the formation of new blood vessels and improve cerebral blood flow [ 16 ]. EVs can also deliver brain-derived neurotrophic factor (BDNF) to the brain and promote the survival and growth of neurons [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

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Engineered extracellular vesicles for ischemic stroke: a systematic review and meta-analysis of preclinical studies

Li,

Yin,

Chen

et al. 2023

J Nanobiotechnol

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Background This systematic review and meta-analysis aimed to evaluate the efficacy of engineered extracellular vesicles (EEVs) in the treatment of ischemic stroke (IS) in preclinical studies and to compare them with natural extracellular vesicles (EVs). The systematic review provides an up-to-date overview of the current state of the literature on the use of EEVs for IS and informs future research in this area. Methods We searched PubMed, EMBASE, Web of Science, Cochrane Library, and Scopus databases for peer-reviewed preclinical studies on the therapeutic effect of EEVs on IS.Databases ranged from the inception to August 1, 2023. The outcome measures included infarct volumes, neurological scores, behavioral scores, apoptosis rates, numbers of neurons, and levels of IL-1β, IL-6, and TNF-α. The CAMARADES checklist was used to assess the quality and bias risks of the studies. All statistical analyses were performed using RevMan 5.4 software. Results A total of 28 studies involving 1760 animals met the inclusion criteria. The results of the meta-analysis showed that compared to natural EVs, EEVs reduced infarct volume (percentage: SMD = -2.33, 95% CI: -2.92, -1.73; size: SMD = -2.36, 95% CI: -4.09, -0.63), improved neurological scores (mNSS: SMD = -1.78, 95% CI: -2.39, -1.17; Zea Longa: SMD = -2.75, 95% CI: -3.79, -1.71), promoted behavioral recovery (rotarod test: SMD = 2.50, 95% CI: 1.81, 3.18; grid-walking test: SMD = -3.45, 95% CI: -5.15, -1.75; adhesive removal test: SMD = -2.60, 95% CI: -4.27, -0.93; morris water maze test: SMD = -3.91, 95% CI: -7.03, -0.79), and reduced the release of proinflammatory factors (IL-1β: SMD = -2.02, 95% CI: -2.77, -1.27; IL-6: SMD = -3.01, 95% CI: -4.47, -1.55; TNF-α: SMD = -2.72, 95% CI: -4.30, -1.13), increasing the number of neurons (apoptosis rate: SMD = -2.24, 95% CI: -3.32, -1.16; the number of neurons: SMD = 3.70, 95% CI: 2.44, 4.96). The funnel plots for the two main outcome measures were asymmetric, indicating publication bias. The median score on the CAMARADES checklist was 7 points (IQR: 6–9). Conclusions This meta-analysis shows that EEVs are superior to natural EVs for the treatment of IS. However, research in this field is still at an early stage, and more research is needed to fully understand the potential therapeutic mechanism of EEVs and their potential use in the treatment of IS. PROSPERO registration number CRD42022368744.

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“…As shown in Fig. 1 and 28 studies [ 17 , 21 – 47 ] ultimately met our criteria and were included in this review. Details of these studies are presented in Table 1 .…”

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Engineered extracellular vesicles for ischemic stroke: a systematic review and meta-analysis of preclinical studies

Li,

Yin,

Chen

et al. 2023

J Nanobiotechnol

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“…Furthermore, NPC-derived EVs could reduce the recruitment of inflammatory-related cells by inhibiting the nuclear factor-κB (NF-κB) pathway and enhance BBB integrity by regulating ATP-binding cassette transporter B1 (ABCB1) and matrix metalloproteinase 9 (MMP-9) [ 119 ]. Additionally, Xu and his teammates found that EVs derived from NPCs could reduce the infarct volume, neurologic deficit score (NDS), neural apoptosis, and ROS production as well as increase the density of dendrites in MCAO mice, possibly through the regulation of the ROS/Nox2 and BDNF/TrkB pathways by miR-210 [ 120 ].…”

Section: Role Of Nvu-evs In Ismentioning

confidence: 99%

“…Additionally, after IS in diabetic mice, miR-126 in EC-EVs could not only promote neurological functional recovery and increase the myelin density, axon density, arterial diameter, and vascular density, but also induce M2 macrophage polarization in the infarct area [ 137 ]. Similarly, miR-126 in EVs derived from endothelial progenitor cells (EPCs) could reduce the infarct size, increase CBF and cerebral microvascular density (MVD), and promote angiogenesis, neurogenesis, and neurological functional recovery after IS in diabetic and healthy mice, possibly via the regulation of the ROS/Nox2 and BDNF/TrkB pathways [ 34 , 120 , 138 , 139 ]. Furthermore, EC-EVs could promote IS recovery in MCAO model rats by increasing NPC migration and proliferation as well as reducing NPC apoptosis [ 140 ].…”

Section: Role Of Nvu-evs In Ismentioning

confidence: 99%

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

Gao,

Liu,

Yue

et al. 2024

Biomolecules

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

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“…Ischemic stroke (IS) is a life-threatening cerebral vascular disease accounting for high disability and mortality worldwide. Emerging recent studies suggest a potential role of EVs in the treatment of IS Indeed, in recent years, various kinds of mammalian cell-derived EVs, such as those derived from mesenchymal stem cells, neural stem cells, type 2 microglia, and brain endothelial cells have been used to treat IS by altering the expression of microRNAs (miRs) in the organism ( Xu et al, 2023 ). However, due to the prohibitive cost of mammalian cell culture, it is difficult to obtain a culture medium for EVs extraction on a large scale in the short term, which has limited the translation of EVs research to the clinic.…”

Section: Good Gmevs: Probiotics-derived Evs and Their Potential Thera...mentioning

confidence: 99%

Emerging therapeutic role of gut microbial extracellular vesicles in neurological disorders

et al. 2023

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Extracellular vesicles (EVs) serve as cell-to-cell and inter-organ communicators by conveying proteins and nucleic acids with regulatory functions. Emerging evidence shows that gut microbial-released EVs play a pivotal role in the gut-brain axis, bidirectional communication, and crosstalk between the gut and the brain. Increasing pre-clinical and clinical evidence suggests that gut bacteria-released EVs are capable of eliciting distinct signaling to the brain with the ability to cross the blood–brain barrier, exerting regulatory function on brain cells such as neurons, astrocytes, and microglia, via their abundant and diversified protein and nucleic acid cargo. Conversely, EVs derived from certain species of bacteria, particularly from gut commensals with probiotic properties, have recently been shown to confer distinct therapeutic effects on various neurological disorders. Thus, gut bacterial EVs may be both a cause of and therapy for neuropathological complications. This review marshals the basic, clinical, and translational studies that significantly contributed to our up-to-date knowledge of the therapeutic potential of gut microbial-derived EVs in treating neurological disorders, including strokes, Alzheimer’s and Parkinson’s disease, and dementia. The review also discusses the newer insights in recent studies focused on developing superior therapeutic microbial EVs via genetic manipulation and/or dietary intervention.

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Combination of EPC-EXs and NPC-EXs with miR-126 and miR-210 overexpression produces better therapeutic effects on ischemic stroke by protecting neurons through the Nox2/ROS and BDNF/TrkB pathways

Cited by 20 publications

References 82 publications

Engineered extracellular vesicles for ischemic stroke: a systematic review and meta-analysis of preclinical studies

Engineered extracellular vesicles for ischemic stroke: a systematic review and meta-analysis of preclinical studies

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

Emerging therapeutic role of gut microbial extracellular vesicles in neurological disorders

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