Exosomes

Nano-Gold and Silver work - since they ride on Exosomes ?

Exosomes guard the Crime Scene
..but why do they leave after 96h ?

Golden Exosomes Selectively Target Brain Pathologies in Neurodegenerative and Neurodevelopmental Disorders
Nano Lett., Article ASAP
DOI: 10.1021/acs.nanolett.8b04148
Publication Date (Web): February 14, 2019

Exosomes, nanovesicles that are secreted by different cell types, enable intercellular communication at local or distant sites. Alhough they have been found to cross the blood brain barrier, their migration and homing abilities within the brain remain unstudied. We have recently developed a method for longitudinal and quantitative in vivo neuroimaging of exosomes based on the superior visualization abilities of classical X-ray computed tomography (CT), combined with gold nanoparticles as labeling agents.

Here, we used this technique to track the migration and homing patterns of intranasally administrated exosomes derived from bone marrow mesenchymal stem cells (MSC-exo) in different brain pathologies, including stroke, autism, Parkinson’s disease, and Alzheimer’s disease.

We found that MSC-exo specifically targeted and accumulated in pathologically relevant murine models brains regions up to 96 h post administration, while in healthy controls they showed a diffuse migration pattern and clearance by 24 h. The neuro-inflammatory signal in pathological brains was highly correlated with MSC-exo accumulation, suggesting that the homing mechanism is inflammatory-driven.

In addition, MSC-exo were selectively uptaken by neuronal cells, but not glial cells, in the pathological regions. Taken together, these findings can significantly promote the application of exosomes for therapy and targeted drug delivery in various brain pathologies.

https://pubs.acs.org/doi/10.1021/acs.nanolett.8b04148
 
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On a side note, and not immediately relevant to ME, here's another example of the versatility of exosomes.

This comes from a newspaper article about a Danish PhD thesis whose author recently won a science communication award (Google translated, bolding mine).
When the parasites, Eline Palm Meldgaard have investigated - the knot, whip and spool worm - have reached a pig, for example through parasitic eggs that have crept into the food, they secrete some transport particles, the so-called exosomes. The exosomes apparently lead some molecules called microRNA into the host cells, and these are the molecules that are potentially capable of blocking or limiting portions of the host's immune response. [...]
Although Eline Palm Meldgaard emphasizes that it is still only "a fascinating thought," her project therefore suggests that the molecules manipulate the immune system not to respond to the worm's presence. They carry the body behind the light. And it is therefore possible that the parasite - which, depending on the species, can be between a couple and up to 40 centimeters - can enjoy the host's hospitality, often for several months.
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The whole article (Danish) is here: https://www.information.dk/2019/04/eline-palm-meldgaard-gaar-angreb-paa-udspekulerede-orme
 
The subject of whether exosomes could carry pathogens came up on another thread. I did a search on exosomes and pathogens and found this paper:

Exosomes in Pathogen Infections: A Bridge to Deliver Molecules and Link Functions by Zhang et al.

Abstract
Exosomes are extracellular vesicles derived from cell endocytosis which act as transmitters between cells. They are composed of proteins, lipids, and RNAs through which they participate in cellular crosstalk. Consequently, they play an important role in health and disease.

Our view is that exosomes exert a bidirectional regulatory effect on pathogen infections by delivering their content.

First, exosomes containing proteins and RNAs derived from pathogens can promote infections in three ways: (1) mediating further infection by transmitting pathogen-related molecules; (2) participating in the immune escape of pathogens; and (3) inhibiting immune responses by favoring immune cell apoptosis.

Second, exosomes play anti-infection roles through: (1) inhibiting pathogen proliferation and infection directly; (2) inducing immune responses such as those related to the function of monocyte-macrophages, NK cells, T cells, and B cells.

We believe that exosomes act as “bridges” during pathogen infections through the mechanisms mentioned above. The purpose of this review is to describe present findings regarding exosomes and pathogen infections, and highlight their enormous potential in clinical diagnosis and treatment.

We discuss two opposite aspects: infection and anti-infection, and we hypothesize a balance between them. At the same time, we elaborate on the role of exosomes in immune regulation.
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I've split it into shorter paragraphs for easier reading. It's an open access paper.


 
The International Society for Extracellular Vesicles (ISEV) held their 2019 annual meeting in Kyoto, Japan from April 24th to 28th. Center member Dr. Ludovic Giloteaux attended the conference to network with international experts on the latest extracellular vesicle (EV) research. Dr. Giloteaux also presented some of our current EV research on cytokine and miRNA profiling of plasma EVs in ME/CFS. Check out the conference program for an overview of what information was covered.
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Code: 
https://www.facebook.com/CornellMECFSCenter/posts/1058494611008644



Direct link to the program for that meeting, https://cdn.ymaws.com/www.isev.org/resource/resmgr/ISEV2019_Final_Program.pdf
 
Not sure where to put this review, and I haven't read all of it, just posting in case someone else is interested.

Extracellular Vesicles in Epstein-Barr Virus’ Life Cycle and Pathogenesis

Mengmeng Zhao et al, Microorganisms 2019, 7(2).

Abstract

Extracellular vesicles (EVs), including exosomes and microvesicles, are evolutionarily conserved phospholidpid membrane-bound entities secreted from most eukaryotic cell types. They carry bioactive cargos such as protein and nucleic acids derived from their cells of origin. Over the past 10 years, they have been attracting increased attention in many fields of life science, representing a new route for intercellular communication.

In this review article, we will discuss the current knowledge of both normal and virally modified EVs in the regulation of Epstein-Barr virus (EBV)’s life cycle and its associated pathogenesis.

https://www.mdpi.com/2076-2607/7/2/48/htm
 
Another paper on Exosomes that I thought appropriate for this thread.

Adipose tissue-derived extracellular vesicles mediate development of metabolic diseases (5Nov2019)
https://link.springer.com/article/10.1007/s00125-019-05014-5
Abstract

Extracellular vesicles (EVs) are submicron-sized lipid envelopes that are produced and released from a parent cell and can be taken up by a recipient cell.

EVs are capable of mediating cellular signalling by carrying nucleic acids, proteins, lipids and cellular metabolites between cells and organs.

Metabolic dysfunction is associated with changes in plasma concentrations of EVs as well as alterations in their EV cargo.

Since EVs can act as messengers between parent and recipient cells, they could be involved in cell-to-cell and organ-to-organ communication in metabolic diseases.

Recent literature has shown that EVs are produced by cells within metabolic tissues, such as adipose tissue, pancreas, muscle and liver. These vesicles have therefore been proposed as a novel intercellular communication mode in systemic metabolic regulation.

In this review, we will describe and discuss the current literature that investigates the role of adipose-derived EVs in the regulation of obesity-associated metabolic disease. We will particularly focus on the EV-dependent communication between adipocytes, the vasculature and immune cells in type 2 diabetes.
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I thought the section on processing of blood to extract exosomes was interesting for those wanting to learn more about the process. Image (C) and the text associated with it below
EJRS_e6UYAAWaOU.jpg

The International Society for Extracellular Vesicles (ISEV) publishes guidelines for the isolation, characterisation and experimental use of EVs [19].The most popular method for EV isolation remains ultracentrifugation, as it is easily accessible, cheap and requires little prior specialist knowledge or equipment.

Ultracentrifugation can co-isolate soluble proteins (cytokines, chemokines and growth factors) and lipoproteins, which carry EV-associated cargo such as miRNAs. Washing of isolated EVs can reduce the level of contamination by soluble proteins and lipoproteins, but ultracentrifugation speeds can alter the morphology of EVs, possibly affecting their biological activity.

Immunoaffinity capture using EV-associated antibodies (CD63, CD81 and CD9) conjugated to magnetic beads allows high-throughput processing of clinical samples but is biased towards the isolation of tetraspanin-expressing EVs [20]. Immunoaffinity capture has the added difficulty of binding EV to beads and limits the utilisation of isolated EV for downstream functional characterisation such as in vivo studies.

Size exclusion chromatography (SEC) of EVs from biological fluids allows soluble proteins to be separated from the EV pool but does not eliminate contamination with lipoproteins, and SEC EV samples often need to be further concentrated for additional EV analysis, such as proteomics [21] (see Text box: Methods of EV isolation and characterisation: principles, advantages and limitations).

EV phenotyping in metabolic disease has revealed a number of dysregulated EV proteins and EV miRNAs from numerous tissue types and plasma from individuals with different types of metabolic dysfunction.
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