Research Re Exosomes and ME/CSF

Gingergrrl

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perrier

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Gingergrrl

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The issue is that one has to keep repeating the treatment; the blood is 'cleaned up' as it were, but whatever is making the stuff which should not be there, returns. But it buys times and gives relief, when it works, and that is worth a good deal.
This is what I can't figure out... plasmapheresis is often used as a diagnostic test for autoimmunity, especially in acute situations where the patient is gravely ill. If the patient experiences immediate relief or improvement from plasmapheresis, it is often indicative of autoimmunity. However, like you said, the relief is short-lived and the PP would have to be done repeatedly (and is not a cure).

What confuses me here though is... do "exosomes", or the issue that Dr. Davis is speaking about, relate to autoimmunity or to something completely unrelated in the blood? That's why I was asking about plasmapheresis b/c if Dr. Davis or others have tried it (in research) and the subjects had a quick but short-lived improvement, this would signal autoimmunity to me. Does this make sense or is this way off?
 

Rufous McKinney

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just what an exosome is and what it does
Its an organelle found inside cells. The cells then are: shipping this organelle out. It then is taking with it: stuff thats presumably needing to be removed or clean up or disposed. Its carrying proteins, DNA RNA and other stuff. Its also involved in communications between cells.

This link seems easier to digest than WIki:

https://bioinformant.com/what-are-exosomes/
 

Research 1st

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Regarding the potential for exosomes in post infectious CFS pathology, please have a look at the following. My edit in bold text. Thank you.

"Similar to other pathogens, retroviruses hijack exosomal proteins as well as other components to increase their spread throughout the body. In addition to this benefit, the resulting changes in recipient cells can be profound leading to disease state and pathologies associated with an infection. To this end, HIV-1 infected macrophages have been shown to have increased number of exosomes and other vesicles secreted from the cell (Kadiu and Gendelman, 2011a,b; Kadiu et al., 2011, 2012). Importantly, these exosomes have been shown to contain various cytokines that induce migration and release of other inflammatory cytokines from recipient cells leading to enhanced HIV-1 infectivity. Moreover, some of the virions shed from infected macrophages have been shown to be associated with large aggregates of exosomes secreted from cells and resulting entrapment of virions has demonstrated enhanced infectivity toward target cells including T cells as compared to free purified virions. Additionally, the proteomic analysis of the exosomes from macrophages has identified proteins required for T cell activation, antigen presentation, and chemotaxis. Similar to these findings, we have also recently identified alteration of proteins and cytokines packaged into exosomes from HTLV-infected cells (Jaworski et al., 2014a). The release of these cytokines packaged into exosomes from HTLV-infected cells can lead to enhanced infectivity in recipient cells as well as neuroinflammation associated with HAM/TSP pathology. Therefore, collectively these data demonstrate multiple potential mechanisms where virally-infected cells control exosome release to assist in viral spread and induction of pathologies. These vesicles can in turn activate naïve cells leading to better uptake of virus and cell to cell transmission of viral particles through viral synapses.

Source: Extracellular vesicles from infected cells: potential for pathogenesis. Schwab et al (2015).

https://www.frontiersin.org/articles/10.3389/fmicb.2015.01132/full
 

wigglethemouse

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Good news - it seems there are some groups at Stanford with exosome experience
Exosome-Total-Isolation-Chip (ExoTIC) Device for Identification of Exosome-based Biomarkers
Researchers at Stanford have developed an inexpensive, rapid and efficient method to isolate a high yield of pure exosomes from a wide range of clinical biofluids. Exosomes are small (30-180nm) cell-derived vesicles that are shed into bodily fluids such as blood, urine and saliva.
Link : http://techfinder.stanford.edu/technologies/S16-048_exosome-total-isolation-chip-exotic

Yang Lab
The laboratory has established a seamless workflow to generate iPSCs, differentiate into iCMs, and investigate the therapeutic role of iCMs reliably both in vitro and in vivo. These exosomes will create a paradigm shift across all medical disciplines. The exosomes from the patient-specific iPSC-derived cells will treat many degenerative disorders by triggering and augmenting endogenous repair.
Link : http://med.stanford.edu/cvmedicine/research/faculty-labs-link/yanglab/research.html
 

sb4

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Wonder if somebody can clear this up for me. Ron said they filtered the blood for large particles and they found it was smaller particles that where causing the problem. He said large particles meant cytokines, etc.

So MVBs/Endosomes are sort of like cells within cells that contain molecules. When the endosome meets the cell exterior wall it opens up and releases the molecules (now called exosomes) into the extra cellular space. These exosomes can then merge with / enter / bind to receptors of other cells.

So if exosomes contain a whole bunch of molecules, such as cytokines, then only the smaller molecules are the problem. What are these smaller molecules?

Can someone explain to me how a virus can hijack an exosomal protein? I understand viruses using cell RNA/DNA to help itself replicate but what is it doing to a single protein? Perhaps it just binds to it to gain entry into a cell, or is it causing it to do a different function?
 

Moof

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So if exosomes contain a whole bunch of molecules, such as cytokines, then only the smaller molecules are the problem. What are these smaller molecules?
As I understand it (and I'm not a scientist), this is the crux of the problem. The researchers may have found the transport mechanism for whatever the 'something in the blood' (SIB) is, but they're no nearer identifying it.

It would certainly be useful to know whether exosomes are the only transport mechanism for SIB, as it could help narrow down the list of possibilities; it's still a huge and complex task, though.

At the moment, it looks as if its real importance could be in offering us a diagnostic test, via the nano needle or another approach. That alone would advance research enormously; not only because it's impossible to find a treatment for a disease when you can't even be sure that all your study participants have it, but because it would give the disease and the research the credibility that it still lacks.
 
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Is there anyone out there that can explain in terms that I can understand just what an exosome is and what it does?

Is this a chemical produced by the human body or an invasion? I have read the Wikipedia explanation and I am more confused than when I started.
An exosome is a little bubble that comes out of a human cell, made out of bits of the cell. So not just a chemical, but lots of different bits of DNA and proteins. And they are "self" not an invasion. They have been discovered recently and they are very small so science remains unsure of their purpose.
 
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@Murph
Once the exosomes leave the cell they must go into the blood stream. Are they then removed by the bodies normal processes, such as liver, Kidneys, etc.? Could the bodies failure to remove them be the problem?
This is a good question. Some are absorbed by other cells (which is why scientists believe they may be beign used as messengers). I am unsure if the liver would kill them off since they are "self". I guess they might just float round in blood til they experience apoptosis?
 
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On the topic of exosomes and potential short-term treatments, two technologies I’ve been eyeing that I believe hold tremendous promise – potentially as “proof of principle” to temporarily treat M.E. patients; and also maybe helpful to bring our most severe patients back from the brink. IMO these could be viable for an M.E. clinical trial, to do big data evaluation on patients before/after cytokine and/or exosome adsorption.

a) Cytosorb’s (CTSO) Cytosorb extracorporeal cytokine adsorber. American company that is going gangbusters in Germany especially, with the Cytosorb used in ICU’s to treat systemic sepsis. Still an early stage biotech, however with doubling year-over-year revenues. As a new poster, I can't post links yet, but will try to shortly. Or you can go to the Cytosorb website and check out their investor presentation and their Cytosorb user’s group (most active in Germany) that waxes poetic on the ability of this cartridge to filter out cytokines from the blood. Quite dramatic physiological responses in these critically ill ICU patients. If M.E. is so closely related to Systemic Inflammatory Response Syndrome and low-grade sepsis, maybe we're ideal candidates too?

b) Aethlon Medical’s Hemopurifier. Started off as an adsorber for viruses, now also targeting cancerous and non-malignant exosomes. You can google Seeking Alpha, and Aethlon for this filing. Will also try to post the link if my health allows later: "We are also investigating the ability of the Hemopurifier to capture glycosylated bacterial toxins and tumor-derived exosomes that promote cancer progression and treatment resistance. Additionally, we are the majority owner of Exosome Sciences, Inc. (ESI), a Company that is focused on the discovery of exosomal biomarkers to diagnose and monitor life-threatening disease conditions that may be current or future therapeutic targets for Aethlon Medical.

Do a search (Control “F”) in this document for “exosomes”, and take a look at all the patents they have on things like “methods for quantifying exosomes”; “methods for removal of exosomes”, etc.

FYI AEMD was one of Time Magazine’s feted ideas a couple of years ago. Lots of folks bought in, then the stock tanked again, so I'm posting from the clinical perspective, not with any investment advice ;) . IMO both of these early-stage biotechs have some maturing to do, but their products are fascinating, and potentially relevant for the M.E. arena.

Both of these technologies (CTSO and AEMD) require a dialysis machine.
 

Rufous McKinney

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They are not cells, so they cannot die. They are: a vescicle produced by cells and secreted into the bloodstream. Now thats all I learned in Cell Physiology 30 years ago.! These technologies are interesting and seem promising.

Last night I read that eppstein barr is visiting the Exosomes. Not sure I wanted to know that.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5666526/