Just stumbled onto this special edition of the Journal Proteomics focused on exosomes. I'm not sure there's aything specific in the below for me/cfs but it's good to see how much work is happening on them.
One great thing about exosomes is they are relevant to the best-funded disease of all: cancer. So we can expect lots of progress in understanding them.
Part II: Special Issue on Extracellular Vesicles and Exosomes
Richard J. Simpson
David W. Greening
First published: 16 April 2019
Part 1 https://onlinelibrary.wiley.com/toc/16159861/2019/19/1-2
Part 2 https://onlinelibrary.wiley.com/toc/16159861/2019/19/8
The ability of secreted extracellular vesicles (EVs) to target and transfer their cargo from donor to acceptor cells to trigger phenotypic changes in the latter has generated immense interest in the biological and commercial sectors. EVs are critical mediators of intercellular communication and regulate pleiotropic biological processes in target cells through horizontal transfer of specifically loaded protein, DNA, lipid, and RNA species. Importantly, EV cargo composition varies depending on cell type and cell environment stress. Not surprisingly, EVs have immense therapeutic potential and their cargos are receiving much attention as potential biomarkers for disease diagnosis and prognosis. EVs are present in most body fluids and as such are attractive non‐invasive candidates for disease diagnostics as well as longitudinal therapeutic response metrics of diseases such as cancer, heart disease, and neurodegeneration, in addition to rejection metrics for renal allografts.
The field of EVs is a rapidly growing area of research, with the identification of new types of EVs, expansion on the cell types or organisms that release EVs and their functions, sub‐populations of EV types, as well as the development of novel approaches to characterize and understand EVs. Characterization of distinct types of EV cargo is of significant interest due to the information this cargo provides with respect to the biogenesis, trafficking, targeting, uptake, and cellular effects of EVs. EVs can be classified into two broad categories: exosomes (endosomal origin) and microparticles (also referred to as shed microvesicles and ectosomes, amongst others), which are derived from blebbing of the plasma membrane. Because it is difficult to separate EV classes (and their subtypes) one from another by conventional separation, they are loosely termed “small EVs” and “large EVs.”
Reviewed previously (Greening et al., Expert Rev. Proteomics 2017, 14, 69), mass spectrometry–based proteomics is a powerful technology for the quantitative identification of protein components of EV classes and their subtypes—information that is fundamental for understanding their biogenesis, function, as well as discovery of stereospecific protein markers that might allow EV subtype discrimination. We present a collection of research and review reports that explore methodologies for the isolation and characterization of EVs, biological insights, and therapeutic potential of EVs released from placental cells, stem/stromal cells, immune cells, tumor cells, as well as pathogens and fungus. This Special Issue published in two parts (January and April) includes reviews, research articles, and viewpoints on the study and understanding of EVs, raising important elements of how different systems regulate the composition of EV content, and subsequently how EVs reprogram their target cell proteome. This includes, but is not limited to cancer biology and oncogenic transformation (https://doi.org/10.1002/pmic.201800169
) and bacteria and their diversity of outer membrane vesicles (https://doi.org/10.1002/pmic.201800209
). Vagner et al. (https://doi.org/10.1002/pmic.201800167
) reviewed how the protein composition reflects EV heterogeneity, directly comparing the protein composition of different EV classes and EV populations derived from the same cell source, as well as different cell types, providing important implications in the understanding of EV biology.
Although exosomal surface membrane proteins (surfaceome) enable target cell recognition and provide an attractive source of disease markers, they are poorly understood. Xu et al. (https://doi.org/10.1002/pmic.201800453
) employed a combination of carbonate extraction and TX114 phase separation and mild proteolysis (proteinase K) to fractionate peripherally associated and integral membrane exosomal proteins. Surfaceome proteins were identified using label‐free quantitative mass spectrometry and membrane bioinformatics. Interestingly, this study revealed RNA binding proteins/ribonucleoproteins and RNA species to be exposed on the outer membrane surface of exosomes. To understand how EVs regulate target cell function, Rai et al. (https://doi.org/10.1002/pmic.201800148
) investigated how exosomes from distinct cancer cell types reprogram the proteome and function of fibroblasts following transfer. Specifically, this study highlights the role of primary and metastatic tumor‐derived exosomes in generating phenotypically and functionally distinct subsets of cancer‐associated fibroblasts that facilitate tumor progression through oncogenic transformation and metabolic reprogramming.
Studies by Hallal et al. (https://doi.org/10.1002/pmic.201800157
) investigated the prognostic potential of vesicular protein cargo (specifically key molecular chaperones) from neurosurgical aspirates of glioblastoma using quantitative mass spectrometry–based proteomics. Further, data independent acquisition (SWATH) by Jayabalan et al. (https://doi.org/10.1002/pmic.201800164
) was used to understand physiological mechanisms associated with insulin resistance during human gestation, specifically identifying differentially abundant exosome cargo associated with gestational diabetes mellitus in comparison to normal glucose tolerance.
The therapeutic potential of EVs, specifically mesenchymal stem/stromal cell–derived vesicles (MSC‐EVs), with van Balkom et al. (https://doi.org/10.1002/pmic.201800163
) identifying a common protein signature that may be useful in ensuring the homogeneity of EV‐specific therapeutics. Further, commentary by Roura et al. (https://doi.org/10.1002/pmic.201800397
) discusses the potential focus areas and issues for rational design and optimization of MSC‐EV production and potency for therapeutics, in addition to Ben‐Hur et al. (https://doi.org/10.1002/pmic.201800170
), discussing the potential for microbial‐associated vesicle‐mediated gene delivery. Nasiri et al (https://doi.org/10.1002/pmic.201800161
). investigated the generation of artificial EVs, termed cell‐derived mimetic nanovesicles (M‐NVs), a promising alternative to EVs for clinical applicability, comparing not only the content of mimetic nanovesicles and how this differed from the parental cell proteome, but further with purified endosomally derived exosomes using a comprehensive characterization and mass spectrometry approach. Further, this study highlights differences in protein post‐translational modifications among M‐NVs, as distinct from exosomes, using a nontargeted informatic approach, specifically showing phosphorylation, ubiquitination, and thiophosphorylation as protein modifications in M‐NVs.
Key reviews of the field include Taylor et al. (https://doi.org/10.1002/pmic.201800165
) highlighting how specific proteins regulate the formation of microvesicles and their drug‐sensitivity capacity in cancer, and Wu et al. (https://doi.org/10.1002/pmic.201800162
), Ruhen et al. (https://doi.org/10.1002/pmic.201800155
), and Choi et al. (https://doi.org/10.1002/pmic.201800169
) providing further insights into EVs and cancer diagnostics. Leading research and guidelines to EV proteomics to cardiovascular disease were highlighted by Barrachina et al., (https://doi.org/10.1002/pmic.201800248
) and reviewed by Barrachina et al., (https://doi.org/10.1002/pmic.201800247
) describing insights into the clinical relevance and potential of novel EV markers identified in the context of cardiovascular disease.
The field of EVs is a rapidly growing area of basic, applied, and biomedical research, with the identification of new types of EVs, their biology and functions, as well as the development of novel approaches to purify, characterize, and understand EVs. This research topic has covered a number of cutting‐edge discoveries in this field—and importantly, how proteomics is advancing key questions in the field. Proteomics now holds the promise of identification, quantification, and validation of EV proteins and determining EV subtype‐specific markers and biological insights in how EVs modulate target cells, directed toward biomedical research and clinical applications. We predict an innovative and bright future for expanding the application of mass spectrometry proteomics to research in the EV biology community. We thank all contributors to this special issue research topic and the referees for their prompt and in‐depth reviews.
Kind regards,this special edition of the Journal Proteomics focused on exosomes: