Classification, Functions, and Clinical Relevance of Extracellular Vesicles

Pol, Edwin van der; Böing, Anita N.; Harrison, Paul; Sturk, Augueste; Nieuwland, Rienk

doi:10.1124/pr.112.005983

Cited by 1,520 publications

(1,390 citation statements)

References 336 publications

(353 reference statements)

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“…In cancer progression ( Figure 3 ), C‐EVs can create a suitable microenvironment by promoting angiogenesis, regulating immunity, and remodeling surrounding tissue, or by laying the foundation for metastasis by forming a premetastatic niche 37, 38, 39, 40. It appears that cancers co‐opt EVs, a natural nanodelivery system, to transfer damaging information by altering the composition of EVs; this ability has inspired scientists to design novel drug therapeutics through reverse engineering.…”

Section: Introductionmentioning

confidence: 99%

Modularized Extracellular Vesicles: The Dawn of Prospective Personalized and Precision Medicine

2018

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Extracellular vesicles (EVs) are ubiquitous nanosized membrane vesicles consisting of a lipid bilayer enclosing proteins and nucleic acids, which are active in intercellular communications. EVs are increasingly seen as a vital component of many biological functions that were once considered to require the direct participation of stem cells. Consequently, transplantation of EVs is gradually becoming considered an alternative to stem cell transplantation due to their significant advantages, including their relatively low probability of neoplastic transformation and abnormal differentiation. However, as research has progressed, it is realized that EVs derived from native‐source cells may have various shortcomings, which can be corrected by modification and optimization. To date, attempts are made to modify or improve almost all the components of EVs, including the lipid bilayer, proteins, and nucleic acids, launching a new era of modularized EV therapy through the “modular design” of EV components. One high‐yield technique, generating EV mimetic nanovesicles, will help to make industrial production of modularized EVs a reality. These modularized EVs have highly customized “modular design” components related to biological function and targeted delivery and are proposed as a promising approach to achieve personalized and precision medicine.

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Section: Introductionmentioning

confidence: 99%

Modularized Extracellular Vesicles: The Dawn of Prospective Personalized and Precision Medicine

2018

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“…This membrane often contains proteins from the parental cell, thus enabling the identification of the cell of origin. In addition, EVs contain biomolecules originating from the parental cells, including RNA and DNA, metabolites and lipids [5]. …”

Section: Basic and Clinical Aspects Of Extracellular Vesiclesmentioning

confidence: 99%

Essentials of extracellular vesicles: posters on basic and clinical aspects of extracellular vesicles

Nieuwland

Falcón‐Pérez

Soekmadji

et al. 2018

J of Extracellular Vesicle

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The past decade has witnessed an exponential development in the field of extracellular vesicles. Sporadic observations have reached a critical level and the scientific community increasingly recognizes the potential biomedical significance of these subcellular structures present in all body fluids as significant components of the cellular secretome. The Educational Committee of the International Society for Extracellular Vesicles prepared two posters (“Basic aspects of extracellular vesicles” and “Clinical aspects of extracellular vesicles”) to provide essential pieces of information on extracellular vesicles at glance for anyone not familiar with the field.

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“…Recent progress in this field shows that urine extracellular vesicles (EVs) are composed of several different subsets of vesicles including exosomes, microvesicles (ectosomes), apoptotic bodies and others [7,8]. The differences of the subclasses are conceptually clear, but it is practically difficult to differentiate them because they share their characteristics such as sizes, shapes and specific markers [9].…”

Section: Introductionmentioning

confidence: 99%

AQP2 in human urine is predominantly localized to exosomes with preserved water channel activities

et al. 2018

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Background AQP2 water channel is critical for urinary concentration in the kidney. Interestingly, AQP2 is abundantly excreted in the urine as extracellular vesicles (EVs), which is known to be a useful biomarker for water-balance disorders although the character of AQP2-enriched EVs is poorly understood including water channel function. Methods Human urine EVs were obtained by a differential centrifugation method. AQP2-bearing EVs were isolated by immunoprecipitation with an AQP2-specific antibody, and the proteins in the EVs were analyzed by LC-MS/MS proteomic analysis. Osmotic water permeability (Pf) of the AQP2-rich EVs was measured by a stopped-flow method monitoring scattered light intensity in response to outwardly directed osmotic gradient. Results Sequential centrifugation of human urine showed that AQP2 was present predominantly (80%) in low-density EVs (160,000 g), whereas negligible amount in high-density EVs (17,000 g). Proteomic analysis of the AQP2-bearing EVs identified 137 proteins, mostly in the endosome pathway, including the components of ESCRT (endosomal sorting complex required transporter)-I, II, III. Pf value of the 160,000 g EVs was 4.75 ± 0.38 × 10 −4 cm s −1 (mean ± SE) with the activation energy of 3.51 kcal mol −1 which was inhibited with 0.3 mM HgCl 2 by 63%, suggesting a channel-mediated water transport. Moreover, Pf value showed a significant correlation with the abundance of AQP2 protein in EVs. Conclusion Taken together, AQP2 is localized predominantly to urinary exosomes with preserved water channel activities.

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Classification, Functions, and Clinical Relevance of Extracellular Vesicles

Cited by 1,520 publications

References 336 publications

Modularized Extracellular Vesicles: The Dawn of Prospective Personalized and Precision Medicine

Modularized Extracellular Vesicles: The Dawn of Prospective Personalized and Precision Medicine

Essentials of extracellular vesicles: posters on basic and clinical aspects of extracellular vesicles

AQP2 in human urine is predominantly localized to exosomes with preserved water channel activities

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