Exosome reporter mice reveal the involvement of exosomes in mediating neuron to astroglia communication in the CNS DOI Creative Commons

Yuqin Men,

Julia Yelick, Shijie Jin

et al.

Nature Communications, Journal Year: 2019, Volume and Issue: 10(1)

Published: Sept. 12, 2019

Abstract Astroglia play active and diverse roles in modulating neuronal/synaptic functions the CNS. How these astroglial are regulated, especially by neuronal signals, remains largely unknown. Exosomes, a major type of extracellular vesicles (EVs) that originate from endosomal intraluminal (ILVs), have emerged as new intercellular communication process. By generating cell-type-specific ILVs/exosome reporter (CD63-GFP f/f ) mice immuno-EM/confocal image analysis, we found CD63-GFP + ILVs primarily localized soma dendrites, but not axonal terminals vitro vivo. Secreted exosomes contain subset microRNAs (miRs) is distinct miR profile neurons. These miRs, neuron-specific miR-124-3p, potentially internalized into astrocytes. MiR-124-3p further up-regulates predominant glutamate transporter GLT1 suppressing GLT1-inhibiting miRs. Our findings suggest previously undescribed exosomal miR-mediated genetic regulation astrocyte functions, opening frontier understanding CNS communication.

Language: Английский

The biology , function , and biomedical applications of exosomes DOI Open Access
Raghu Kalluri, Valerie S. LeBleu

Science, Journal Year: 2020, Volume and Issue: 367(6478)

Published: Feb. 7, 2020

Clinical uses of cellular communication Exosomes are a type extracellular vesicle that contain constituents (protein, DNA, and RNA) the cells secrete them. They taken up by distant cells, where they can affect cell function behavior. Intercellular through exosomes seems to be involved in pathogenesis various disorders, including cancer, neurodegeneration, inflammatory diseases. In Review, Kalluri LeBleu discuss biogenesis disease, highlighting areas more research is needed. also potential clinical applications exosome profiling for diagnostics exosome-mediated delivery therapeutics target disease cells. Science , this issue p. eaau6977

Language: Английский

Citations

7324
Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches DOI Creative Commons
Joshua A Welsh, Deborah C. I. Goberdhan, Lorraine O’Driscoll

et al.

Journal of Extracellular Vesicles, Journal Year: 2024, Volume and Issue: 13(2)

Published: Feb. 1, 2024

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of cell origin and change functions phenotypes other cells. These features indicate strong biomarker therapeutic potential have generated broad interest, as evidenced by steady year-on-year increase in numbers scientific publications about EVs. Important advances been made EV metrology understanding applying biology. However, hurdles remain to realising EVs domains ranging from basic biology clinical applications due challenges nomenclature, separation non-vesicular extracellular particles, characterisation functional studies. To address opportunities this rapidly evolving field, International Society for Vesicles (ISEV) updates its 'Minimal Information Studies Vesicles', which was first published 2014 then 2018 MISEV2014 MISEV2018, respectively. The goal current document, MISEV2023, is provide researchers with an updated snapshot available approaches advantages limitations production, multiple sources, including culture, body fluids solid tissues. In addition presenting latest art principles research, document also covers advanced techniques that are currently expanding boundaries field. MISEV2023 includes new sections on release uptake a brief discussion vivo study Compiling feedback ISEV expert task forces more than 1000 researchers, conveys research facilitate robust discoveries move field forward even rapidly.

Language: Английский

Citations

1313
Extracellular vesicles in cancer — implications for future improvements in cancer care DOI
Rong Xu, Alin Rai, Maoshan Chen

et al.

Nature Reviews Clinical Oncology, Journal Year: 2018, Volume and Issue: 15(10), P. 617 - 638

Published: May 23, 2018

Language: Английский

Citations

1239
Exosome Theranostics: Biology and Translational Medicine DOI Creative Commons
Chuanjiang He,

Shu Zheng,

Yan Luo

et al.

Theranostics, Journal Year: 2017, Volume and Issue: 8(1), P. 237 - 255

Published: Nov. 20, 2017

Exosomes are common membrane-bound nanovesicles that contain diverse biomolecules, such as lipids, proteins, and nucleic acids.Exosomes derived from cells through exocytosis, ingested by target cells, can transfer biological signals between local or distant cells.Exosome secretion is a constitutive phenomenon involved in both physiological pathological processes determines the exosomal surface molecules contents.Hence, we exploit exosomes biomarkers, vaccines drug carriers modify them rationally for therapeutic interventions.However, it still challenge to identify, isolate quantify accurately, efficiently selectively.Further studies on will explore their potential translational medicine provide new avenues creation of effective clinical diagnostics strategies; use these applications be called exosome theranostics.This review describes fundamental formation uptake.In addition, roles biology also illustrated with focus how exploited engineered powerful tools medicine.

Language: Английский

Citations

1026
Hallmarks of Brain Aging: Adaptive and Pathological Modification by Metabolic States DOI Creative Commons
Mark P. Mattson, Thiruma V. Arumugam

Cell Metabolism, Journal Year: 2018, Volume and Issue: 27(6), P. 1176 - 1199

Published: June 1, 2018

Language: Английский

Citations

944
Exosomes: Therapy delivery tools and biomarkers of diseases DOI Creative Commons
Lucio Barile, Giuseppe Vassalli

Pharmacology & Therapeutics, Journal Year: 2017, Volume and Issue: 174, P. 63 - 78

Published: Feb. 13, 2017

Language: Английский

Citations

930
The Neuronal Gene Arc Encodes a Repurposed Retrotransposon Gag Protein that Mediates Intercellular RNA Transfer DOI Creative Commons

Elissa D. Pastuzyn,

Cameron E. Day,

Rachel B. Kearns

et al.

Cell, Journal Year: 2018, Volume and Issue: 172(1-2), P. 275 - 288.e18

Published: Jan. 1, 2018

Language: Английский

Citations

514
Evidence-Based Clinical Use of Nanoscale Extracellular Vesicles in Nanomedicine DOI
Stefano Fais, Lorraine O’Driscoll, Francesc E. Borràs

et al.

ACS Nano, Journal Year: 2016, Volume and Issue: 10(4), P. 3886 - 3899

Published: March 15, 2016

Recent research has demonstrated that all body fluids assessed contain substantial amounts of vesicles range in size from 30 to 1000 nm and are surrounded by phospholipid membranes containing different membrane microdomains such as lipid rafts caveolae. The most prominent representatives these so-called extracellular (EVs) nanosized exosomes (70-150 nm), which derivatives the endosomal system, microvesicles (100-1000 produced outward budding plasma membrane. Nanosized EVs released almost cell types mediate targeted intercellular communication under physiological pathophysiological conditions. Containing cell-type-specific signatures, have been proposed biomarkers a variety diseases. Furthermore, according their physical functions, selected used therapeutic agents immune therapy, vaccination trials, regenerative medicine, drug delivery. Undoubtedly, rapidly emerging field basic applied EV will significantly influence biomedicinal landscape future. In this Perspective, we, network European scientists clinical, academic, industry settings collaborating through H2020 Cooperation Science Technology (COST) program Network on Microvesicles Exosomes Health Disease (ME-HAD), demonstrate high potential for both diagnostic (i.e., theranostic) areas nanomedicine.

Language: Английский

Citations

442
Bidirectional Microglia–Neuron Communication in Health and Disease DOI Creative Commons

Zsuzsanna Szepesi,

Oscar Manouchehrian, Sara Bachiller

et al.

Frontiers in Cellular Neuroscience, Journal Year: 2018, Volume and Issue: 12

Published: Sept. 27, 2018

Microglia are ramified cells that exhibit highly motile processes, which continuously survey the brain parenchyma and react to any insult CNS homeostasis. Although microglia have long been recognized as a crucial player in generating maintaining inflammatory responses CNS, now it has become clear, their function much more diverse, particularly healthy brain. The innate immune response phagocytosis represent only little segment of functional repertoire also includes maintenance biochemical homeostasis, neuronal circuit maturation during development experience- dependent remodeling circuits adult Being equipped by numerous receptors cell surface molecules can perform bidirectional interactions with other types CNS. There is accumulating evidence showing neurons inform about status thus capable controlling microglial activation motility while modulate activities. This review addresses topic: how communicate brain, including fractalkine signaling, secreted soluble factors extracellular vesicles. We summarize current state knowledge physiological role mature further highlight contribution pathologies such Alzheimer's Parkinson's disease, ischemia, traumatic injury, tumour well neuropsychiatric diseases (depression, bipolar disorder schizophrenia).

Language: Английский

Citations

399
M2 microglia-derived exosomes protect the mouse brain from ischemia-reperfusion injury via exosomal miR-124 DOI Creative Commons
Yaying Song, Zongwei Li, Tingting He

et al.

Theranostics, Journal Year: 2019, Volume and Issue: 9(10), P. 2910 - 2923

Published: Jan. 1, 2019

Rationale: Microglia play a critical role in modulating cell death and neurobehavioral recovery response to brain injury either by direct cell-cell interaction or indirect secretion of trophic factors.Exosomes secreted from cells are well documented deliver bioactive molecules recipient modulate function.Here, we aimed identify whether M2 microglia exert neuroprotection after ischemic attack through an exosome-mediated interaction.Methods: microglia-derived exosomes were intravenously injected into the mouse immediately middle cerebral artery occlusion.Infarct volume, neurological score, neuronal apoptosis examined 3 days attack.Exosome RNA target protein expression levels neurons tissue determined for mechanistic study.Results: Our results showed that taken up vitro vivo.M2 exosome treatment attenuated oxygen-glucose deprivation (p<0.05).In vivo significantly reduced infarct volume behavioral deficits transient ischemia (p<0.05),whereas injection miR-124 knockdown (miR-124k/d) partly reversed neuroprotective effect.Our study further demonstrated ubiquitin-specific protease 14 (USP14) was downstream miR-124.Injection miR-124k/d plus USP14 inhibitor, IU1, achieved comparable effect as alone.Conclusions: We promoted survival via exosomal its USP14.M2 represent promising avenue treating stroke.

Language: Английский

Citations

387