The role of small extracellular vesicles in cerebral and myocardial ischemia—Molecular signals, treatment targets, and future clinical translation

Zheng, Xuan; Hermann, Dirk M.; Bähr, Mathias; Doeppner, Thorsten R.

doi:10.1002/stem.3329

Cited by 27 publications

(21 citation statements)

References 120 publications

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“…Extracellular vesicles (EVs) are membrane particles secreted by most cells that constitute major vehicles for intercellular communication. In response to a stroke, EVs are released into the blood from brain cells and other organs [1][2][3][4][5]. These EVs can carry proteins and miRNAs that reveal important information regarding damage, protection, and the repair process after brain ischaemia, as well as stroke outcomes [6][7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Circulating Extracellular Vesicle Proteins and MicroRNA Profiles in Subcortical and Cortical-Subcortical Ischaemic Stroke

et al. 2021

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In order to investigate the role of circulating extracellular vesicles (EVs), proteins, and microRNAs as damage and repair markers in ischaemic stroke depending on its topography, subcortical (SC), and cortical-subcortical (CSC) involvement, we quantified the total amount of EVs using an enzyme-linked immunosorbent assay technique and analysed their global protein content using proteomics. We also employed a polymerase chain reaction to evaluate the circulating microRNA profile. The study included 81 patients with ischaemic stroke (26 SC and 55 CSC) and 22 healthy controls (HCs). No differences were found in circulating EV levels between the SC, CSC, and HC groups. We detected the specific expression of C1QA and Casp14 in the EVs of patients with CSC ischaemic stroke and the specific expression of ANXA2 in the EVs of patients with SC involvement. Patients with CSC ischaemic stroke showed a lower expression of miR-15a, miR-424, miR-100, and miR-339 compared with those with SC ischaemic stroke, and the levels of miR-339, miR-100, miR-199a, miR-369a, miR-424, and miR-15a were lower than those of the HCs. Circulating EV proteins and microRNAs from patients with CSC ischaemic stroke could be considered markers of neurite outgrowth, neurogenesis, inflammation process, and atherosclerosis. On the other hand, EV proteins and microRNAs from patients with SC ischaemic stroke might be markers of an anti-inflammatory process and blood–brain barrier disruption reduction.

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Section: Introductionmentioning

confidence: 99%

Circulating Extracellular Vesicle Proteins and MicroRNA Profiles in Subcortical and Cortical-Subcortical Ischaemic Stroke

et al. 2021

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“…The primary standard of ischemic stroke care is the delivery of tissue plasminogen activator (tPA); interestingly, the addition of exosomes to tPA treatment significantly improved functional outcome following stroke compared to tPA treatment alone [313,317]. Delivery of MSC-Exos in stroke models leads to long-term neuroprotection, improved neurogenesis and neurovascular remodeling, as well as enhanced behavioral and neurological performances in motor function, coordination, sensorimotor, and spatial learning [136,317,324,[326][327][328][329][330]. Varied contents of exosomes have been shown to aid recuperation, from growth factors such as VEGF to microRNAs [46,331].…”

Section: Brain Injurymentioning

confidence: 99%

“…Varied contents of exosomes have been shown to aid recuperation, from growth factors such as VEGF to microRNAs [46,331]. Zheng et al identified that miR-25 in MSC-Exos improved cell viability following stroke through modulation of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3, while in a model of middle cerebral artery occlusion, miR-133b secreted from MSCs led to improved neurogenesis and stroke recovery [46,310,311,330]. Similar to studies in TBI, MSC-Exos can improve recovery through modulation of inflammation [43,136,310,313,328].…”

Section: Brain Injurymentioning

confidence: 99%

Mesenchymal Stem Cell-Derived Exosomes: Applications in Regenerative Medicine

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Suo

2021

Cells

242

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Exosomes are a type of extracellular vesicles, produced within multivesicular bodies, that are then released into the extracellular space through a merging of the multivesicular body with the plasma membrane. These vesicles are secreted by almost all cell types to aid in a vast array of cellular functions, including intercellular communication, cell differentiation and proliferation, angiogenesis, stress response, and immune signaling. This ability to contribute to several distinct processes is due to the complexity of exosomes, as they carry a multitude of signaling moieties, including proteins, lipids, cell surface receptors, enzymes, cytokines, transcription factors, and nucleic acids. The favorable biological properties of exosomes including biocompatibility, stability, low toxicity, and proficient exchange of molecular cargos make exosomes prime candidates for tissue engineering and regenerative medicine. Exploring the functions and molecular payloads of exosomes can facilitate tissue regeneration therapies and provide mechanistic insight into paracrine modulation of cellular activities. In this review, we summarize the current knowledge of exosome biogenesis, composition, and isolation methods. We also discuss emerging healing properties of exosomes and exosomal cargos, such as microRNAs, in brain injuries, cardiovascular disease, and COVID-19 amongst others. Overall, this review highlights the burgeoning roles and potential applications of exosomes in regenerative medicine.

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“…Cancer therapy [317] Exosomes from lung carcinoma cells [318] EVs from Staphylococcus aureus Intracellular delivery of antibiotics for intracellular pathogen-associated complications treatment [319] Exosomes from breast cancer Quantum dots of vanadium carbide Cancer photothermal therapy [320] Exosomes from hepatocellular carcinoma Silver and iron NCs Cancer bioimaging [321] Exosomes from macrophages SPIONs and curcumin Synergistic antitumor therapy in gliomas [322] Exosomes from plasma Superparamagnetic magnetite colloidal nanocrystal clusters Cancer treatment [323] EVs from KB cells Zinc oxide NCs Cancer treatment [324] Since EVs are remarkably involved in genetic information transfer in normal and pathological states [325][326][327], it is not difficult to see their potential as engineered nucleic acids carriers for drug the treatment of ischemic stroke, myocardial infarction [328], traumatic brain injuries [329], and liver fibrosis [330].…”

Section: Plga Npsmentioning

confidence: 99%

Lipid-Based Nanovesicular Drug Delivery Systems

et al. 2021

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In designing a new drug, considering the preferred route of administration, various requirements must be fulfilled. Active molecules pharmacokinetics should be reliable with a valuable drug profile as well as well-tolerated. Over the past 20 years, nanotechnologies have provided alternative and complementary solutions to those of an exclusively pharmaceutical chemical nature since scientists and clinicians invested in the optimization of materials and methods capable of regulating effective drug delivery at the nanometer scale. Among the many drug delivery carriers, lipid nano vesicular ones successfully support clinical candidates approaching such problems as insolubility, biodegradation, and difficulty in overcoming the skin and biological barriers such as the blood–brain one. In this review, the authors discussed the structure, the biochemical composition, and the drug delivery applications of lipid nanovesicular carriers, namely, niosomes, proniosomes, ethosomes, transferosomes, pharmacosomes, ufasomes, phytosomes, catanionic vesicles, and extracellular vesicles.

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The role of small extracellular vesicles in cerebral and myocardial ischemia—Molecular signals, treatment targets, and future clinical translation

Cited by 27 publications

References 120 publications

Circulating Extracellular Vesicle Proteins and MicroRNA Profiles in Subcortical and Cortical-Subcortical Ischaemic Stroke

Circulating Extracellular Vesicle Proteins and MicroRNA Profiles in Subcortical and Cortical-Subcortical Ischaemic Stroke

Mesenchymal Stem Cell-Derived Exosomes: Applications in Regenerative Medicine

Lipid-Based Nanovesicular Drug Delivery Systems

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