Neuroprotective effects of intranasal extracellular vesicles from human platelet concentrates supernatants in traumatic brain injury and Parkinson’s disease models

Journal of Biomedical Science, Journal Year: 2024, Volume and Issue: 31(1)

Published: Sept. 5, 2024

The burgeoning field of regenerative medicine has significantly advanced with recent findings on biotherapies using human platelet lysates (HPLs), derived from clinical-grade concentrates (PCs), for treating brain disorders. These developments have opened new translational research avenues to explore the neuroprotective effects platelet-extracellular vesicles (PEVs). Their potential in managing neurodegenerative conditions like traumatic injury (TBI) and Parkinson's disease (PD) warrants further exploration. We aimed here characterize composition a PEV preparation isolated concentrate (PC) supernatant, determine its neurorestorative cellular animal models TBI PD.

Language: Английский

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Engineering of exosome-liposome hybrid-based theranostic nanomedicines for NIR-II fluorescence imaging-guided and targeted NIR-II photothermal therapy of subcutaneous glioblastoma

Colloids and Surfaces B Biointerfaces, Journal Year: 2024, Volume and Issue: 245, P. 114258 - 114258

Published: Sept. 19, 2024

Language: Английский

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An Overview on the Physiopathology of the Blood–Brain Barrier and the Lipid-Based Nanocarriers for Central Nervous System Delivery

Pharmaceutics, Journal Year: 2024, Volume and Issue: 16(7), P. 849 - 849

Published: June 22, 2024

The state of well-being and health our body is regulated by the fine osmotic biochemical balance established between cells different tissues, organs, systems. Specific districts human are defined, kept in correct functioning, and, therefore, protected from exogenous or endogenous insults both mechanical, physical, biological nature presence barrier In addition to placental barrier, which even acts as a linker two organisms, mother fetus, all barriers, including blood-brain (BBB), blood-retinal blood-nerve blood-lymph blood-cerebrospinal fluid operate maintain physiological homeostasis within tissues organs. From pharmaceutical point view, most challenging undoubtedly BBB, since its notably complicates treatment brain disorders. BBB action can impair delivery chemical drugs biopharmaceuticals into brain, reducing their therapeutic efficacy and/or increasing unwanted bioaccumulation surrounding healthy tissues. Recent nanotechnological innovation provides advanced biomaterials ad hoc customized engineering functionalization methods able assist brain-targeted drug delivery. this context, lipid nanocarriers, synthetic (liposomes, solid nanoparticles, nanoemulsions, nanostructured carriers, niosomes, proniosomes, cubosomes) cell-derived ones (extracellular vesicles cell membrane-derived nanocarriers), considered one successful systems due reasonable biocompatibility ability cross BBB. This review aims provide complete up-to-date view on varied whether FDA-approved, involved clinical trials, used vitro vivo studies, for inflammatory, cancerous, infectious diseases.

Language: Английский

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Profiling biomanufactured extracellular vesicles of human forebrain spheroids in a Vertical‐Wheel Bioreactor

Journal of Extracellular Biology, Journal Year: 2024, Volume and Issue: 3(9)

Published: Aug. 28, 2024

Abstract Extracellular vesicles (EVs) secreted by human brain cells have great potential as cell‐free therapies in various diseases, including stroke. However, because of the significant amount EVs needed preclinical and clinical trials, EV application is still challenging. Vertical‐Wheel Bioreactors (VWBRs) designed features that allow for scaling up generation forebrain spheroid under low shear stress. In this study, secretion spheroids derived from induced pluripotent stem 3D aggregates on Synthemax II microcarriers VWBRs were investigated with static aggregate culture a control. The characterized metabolite transcriptome analysis. isolated nanoparticle tracking analysis, electron microscopy, Western blot. cargo was analyzed using proteomics miRNA sequencing. vitro functional assays an oxygen glucose‐deprived stroke model conducted. Proof concept vivo study performed, too. Human differentiated showed higher growth rate than aggregates. Microcarrier had lower glucose consumption per million glycolysis gene expression but biogenesis genes. three conditions no differences size, yields high to microcarrier cultures, dynamic aggregates, enriched proteins (proteomics) miRNAs (miRNA‐seq), promoting axon guidance, reducing apoptosis, scavenging reactive species, regulating immune responses. demonstrated ability improve recovery vivo. differentiation VWBR significantly increased (up 240–750 fold) compared due microenvironment metabolism change. biomanufactured exosomal characteristics more therapeutic are assays, which paves way future studies.

Language: Английский

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Brain innate immune response via miRNA-TLR7 sensing in polymicrobial sepsis

Brain Behavior and Immunity, Journal Year: 2021, Volume and Issue: 100, P. 10 - 24

Published: Nov. 19, 2021

Sepsis-associated encephalopathy (SAE) occurs in sepsis survivors and is associated with breakdown of the blood–brain barrier (BBB), brain inflammation, neurological dysfunction. We have previously identified a group extracellular microRNAs (ex-miRNAs), such as miR-146a-5p, that were upregulated plasma septic mice human, capable inducing potent pro-inflammatory cytokines complements. Here, we established clinically relevant mouse model SAE investigated role miRNAs their sensor Toll-like receptor 7 (TLR7) inflammation observed BBB disruption profound neuroinflammatory responses for up to 14 days post-sepsis; these included increased production, microglial expansion, peripheral leukocyte accumulation CNS. In battery neurobehavioral tests, displayed impairment motor coordination function. Sepsis significantly RNA miRNA levels days, miR-146a-5p. Exogenously added miR-146a-5p induces innate immune both cultured microglia/astrocytes intact via TLR7-dependent manner. Moreover, genetically deficient miR-146a showed reduced monocytes neutrophils compared WT after sepsis. Finally, ablation TLR7 TLR7-/- preserved integrity, expansion accumulation, attenuated GSK3β signaling brain, but did not improve recovery following Taken together, data establish an important sensing sepsis-induced inflammation.

Language: Английский

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Stem cell-derived extracellular vesicle therapy for acute brain insults and neurodegenerative diseases

BMB Reports, Journal Year: 2022, Volume and Issue: 55(1), P. 20 - 29

Published: Jan. 28, 2022

Other SectionsABSTRACTINTRODUCTIONADVANTAGES OF STEM CELL-DERIVED EXTRACELLULAR VESICLES OVER OTHER THERAPEUTIC STRATEGIESAPPLICATIONS IN BRAIN DISEASESLIMITATIONS CURRENT MSC-EV THERAPEUTICSENHANCING THE EFFICACY VESICLESCLINICAL SCALE PRODUCTION VESICLESCONCLUSIONSACKNOWLEDGEMENTSCONFLICTS INTERESTFIGURESTABLEREFERENCES

Language: Английский

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The complexity of extracellular vesicles: Bridging the gap between cellular communication and neuropathology

Journal of Neurochemistry, Journal Year: 2024, Volume and Issue: unknown

Published: April 22, 2024

Abstract Brain‐derived extracellular vesicles (EVs) serve a prominent role in maintaining homeostasis and contributing to pathology health disease. This review establishes crucial link between physiological processes leading EV biogenesis their impacts on EVs are involved the clearance transport of proteins nucleic acids, responding changes cellular associated with neurodegeneration, including autophagic disruption, organellar dysfunction, aging, other cell stresses. In neurodegenerative disorders (e.g., Alzheimer's disease, Parkinson's etc.), contribute spread pathological like amyloid β, tau, ɑ‐synuclein, prions, TDP‐43, exacerbating neurodegeneration accelerating disease progression. Despite evidence for both neuropathological neuroprotective effects EVs, mechanistic switch functions remains elusive, warranting further research into involvement Moreover, owing innate ability traverse blood–brain barrier ubiquitous nature, emerge as promising candidates novel diagnostic therapeutic strategies. The uniquely positions itself at intersection biology, neurophysiology, neuropathology, offering insights diverse biological roles

Language: Английский

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Extracellular vesicles as nanotheranostic platforms for targeted neurological disorder interventions

Nano Convergence, Journal Year: 2024, Volume and Issue: 11(1)

Published: May 13, 2024

Abstract Central Nervous System (CNS) disorders represent a profound public health challenge that affects millions of people around the world. Diseases such as Alzheimer’s disease (AD), Parkinson’s (PD), and traumatic brain injury (TBI) exemplify complexities diversities complicate their early detection development effective treatments. Amid these challenges, emergence nanotechnology extracellular vesicles (EVs) signals new dawn for treating diagnosing CNS ailments. EVs are cellularly derived lipid bilayer nanosized particles pivotal in intercellular communication within have potential to revolutionize targeted therapeutic delivery identification novel biomarkers. Integrating with amplifies diagnostic capabilities, opening avenues managing diseases. This review focuses on examining fascinating interplay between theranostics. Through highlighting remarkable advancements unique methodologies, we aim offer valuable perspectives how approaches can bring about revolutionary change management. The objective is harness distinctive attributes forge personalized, efficient interventions disorders, thereby providing beacon hope affected individuals. In short, confluence heralds promising frontier impactful treatments against diseases, which continue pose significant challenges. By focusing personalized powerful methods, might improve quality patients.

Language: Английский

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Parkinson’s associated protein DJ-1 regulates intercellular communication via extracellular vesicles in oxidative stress.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 10, 2025

Mutations in DJ-1 cause autosomal recessive Parkinson’s disease. Several functions have been attributed to DJ-1, including a key role the protection from oxidative stress, however how this protein contributes PD pathogenesis is still unclear. Recently, has identified at higher concentration extracellular vesicles (EV) biological fluids of patients, providing link between EV and associated with PD. were isolated medium control rotenone-treated wild-type KO differentiated SH-SY5Y cells, their number was evaluated by flow cytometry proteomic signature cargo investigated mass spectrometry analysis. Migration THP-1 derived macrophages used read out for functional EV. The results obtained validated iPSC-derived neuronal cells. We an altered response rotenone cells compared wild-type. Mass analysis 116 proteins significantly different concentrations two genotypes, suggesting stress. Additionally, we showed that alters ability stimulate macrophage migration, thus implying consequences absence mediated confirmed neurons lacking isogenic controls. Our indicate clear intercellular communication underlying new function may be relevant pathogenesis.

Language: Английский

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Native and Engineered Extracellular Vesicles for the Treatment of Acute Lung Injury and Acute Respiratory Distress Syndrome

Small Science, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 26, 2025

Extracellular vesicles (EVs) are lipid bilayer nanoparticles naturally released from cells, playing a crucial role in intercellular communication. They modulate gene expression and regulate physiological pathological processes, including acute lung injury (ALI) respiratory distress syndrome (ARDS). Research has shown that EVs contain variety of active components, biocompatible small size, do not trigger immune rejection, making the infusion exogenous promising therapeutic tool. With further research, engineering strategies have been proposed to enhance clinical potential EVs. These involve modifying either donor cells secrete or themselves can be engineered circumvent limitations native In this review, an overview biological properties is provided current treating ALI/ARDS, along with latest research findings, summarized. The challenges opportunities for translation as novel tool also discussed, offering new insights into treatment ALI/ARDS using EV technology.

Language: Английский

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