Characterizing Extracellular Vesicles and Their Diverse RNA Contents DOI Creative Commons
Eren M. Veziroglu, George I. Mias

Frontiers in Genetics, Journal Year: 2020, Volume and Issue: 11

Published: July 17, 2020

Cells release nanometer-scale, lipid bilayer-enclosed biomolecular packages (extracellular vesicles; EVs) into their surrounding environment. EVs are hypothesized to be intercellular communication agents that regulate physiological states by transporting biomolecules between near and distant cells. The research community has consistently advocated for the importance of RNA contents in demonstrating that: 1) EV-related can detected a liquid biopsy, 2) disease significantly alter contents, 3) sensitive specific biopsies implemented precision medicine settings measuring EV-derived contents. Furthermore, have medical potential beyond diagnostics. Both natural engineered being investigated therapeutic applications such as regenerative drug delivery agents. This review focuses specifically on EV characterization, analysis content, functional implications. NIH extracellular (ERC) program catapulted human from an profiling standpoint standardizing pipeline working with transcriptomics data, creating centralized database scientific community. There currently thousands RNA-sequencing profiles hosted Extracellular Atlas alone \citep{Murillo2019}, encompassing variety biofluid types health conditions. While number significant discoveries been made through these studies individually, integrative analyses data thus far limited. A primary focus ERC over next five years is bring higher resolution tools so investigators isolate analyze sub-populations, ultimately single sourced discrete cell types, tissues, complex biofluids. Higher techniques will essential evaluating roles circulating at level which impacts clinical decision making. We expect advances microfluidic technologies drive near-term innovation about diverse EVs. Long-term translation EV-based mainstay diagnostic tool depend upon identifying robust patterns genetic material correlate change status.

Language: Английский

Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines DOI Creative Commons
Clotilde Théry, Kenneth W. Witwer, Elena Aïkawa

et al.

Journal of Extracellular Vesicles, Journal Year: 2018, Volume and Issue: 7(1)

Published: Nov. 23, 2018

ABSTRACT The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions extracellular vesicles (EVs), collective term covering various subtypes cell‐released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, many other names. However, specific issues arise when working with these entities, whose size amount often make them difficult to obtain as relatively pure preparations, characterize properly. International Society for Extracellular Vesicles (ISEV) proposed Minimal Information Studies (“MISEV”) guidelines field 2014. We now update “MISEV2014” based on evolution knowledge four years. An important point consider is that ascribing function EVs general, or EVs, requires reporting information beyond mere description crude, potentially contaminated, heterogeneous preparation. For example, claims exosomes are endowed exquisite activities remain support experimentally, given our still limited their molecular machineries biogenesis release, compared biophysically similar EVs. MISEV2018 include tables outlines suggested protocols steps follow document EV‐associated functional activities. Finally, checklist provided summaries key points.

Language: Английский

Citations

8920
Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell-to-cell communication DOI
Mathilde Mathieu, Lorena Martín‐Jaular, Grégory Lavieu

et al.

Nature Cell Biology, Journal Year: 2018, Volume and Issue: 21(1), P. 9 - 17

Published: Dec. 11, 2018

Language: Английский

Citations

3057
RNA delivery by extracellular vesicles in mammalian cells and its applications DOI Open Access
Killian P. O’Brien, Koen Breyne, Stefano Ughetto

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2020, Volume and Issue: 21(10), P. 585 - 606

Published: May 26, 2020

Language: Английский

Citations

1418
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

1268
Progress, opportunity, and perspective on exosome isolation - efforts for efficient exosome-based theranostics DOI Creative Commons

Dongbin Yang,

Weihong Zhang,

Huanyun Zhang

et al.

Theranostics, Journal Year: 2020, Volume and Issue: 10(8), P. 3684 - 3707

Published: Jan. 1, 2020

Exosomes are small extracellular vesicles with diameters of 30-150 nm.In both physiological and pathological conditions, nearly all types cells can release exosomes, which play important roles in cell communication epigenetic regulation by transporting crucial protein genetic materials such as miRNA, mRNA, DNA.Consequently, exosome-based disease diagnosis therapeutic methods have been intensively investigated.However, any natural science field, the in-depth investigation exosomes relies heavily on technological advances.Historically, two main technical hindrances that restricted basic applied researches include, first, how to simplify extraction improve yield and, second, effectively distinguish from other vesicles, especially functional microvesicles.Over past few decades, although a standardized exosome isolation method has still not become available, number techniques established through exploration biochemical physicochemical features exosomes.In this work, comprehensively analyzing progresses separation strategies, we provide panoramic view current techniques, providing perspectives toward development novel approaches for high-efficient various biological matrices.In addition, perspective therapeutics, emphasize issue quantitative microvesicle separation.

Language: Английский

Citations

747
Quality and efficiency assessment of six extracellular vesicle isolation methods by nano‐flow cytometry DOI Creative Commons
Ye Tian,

Manfei Gong,

Yunyun Hu

et al.

Journal of Extracellular Vesicles, Journal Year: 2019, Volume and Issue: 9(1)

Published: Nov. 29, 2019

ABSTRACT Extracellular vesicles (EVs) have sparked tremendous interest owing to their prominent potential in diagnostics and therapeutics. Isolation of EVs from complex biological fluids with high purity is essential the accurate analysis EV cargo. Unfortunately, generally used isolation techniques do not offer good separation non‐EV contaminants. Hence, it important a standardized method characterise properties preparations, including size distribution, particle concentration, phenotype. Employing laboratory‐built nano‐flow cytometer (nFCM) that enables multiparameter single as small 40 nm, here we report new benchmark quality efficiency assessment isolated plasma, one most difficult body work with. The performance five widely commercial kits was examined compared traditional differential ultracentrifugation (UC). Two four orders magnitude higher concentrations were observed for preparations platelet‐free plasma (PFP) by when preparation UC, yet much lower. Meanwhile, distribution profiles closely resembled those PFP whereas UC showed broader at relatively large size. When these isolate vesicle‐depleted (VD‐PFP), comparable counts obtained corresponding PFP, which confirmed again quantity non‐vesicular As CD9, CD63 CD81 also exist matrix, single‐particle phenotyping offers distinct advantage validation ensemble‐averaged approaches, such Western blot analysis. nFCM allows us compare different without prejudice.

Language: Английский

Citations

470
Technologies and Standardization in Research on Extracellular Vesicles DOI Creative Commons
Srujan Gandham, Xianyi Su, Jacqueline Wood

et al.

Trends in biotechnology, Journal Year: 2020, Volume and Issue: 38(10), P. 1066 - 1098

Published: June 18, 2020

Extracellular vesicles (EVs) are phospholipid bilayer membrane-enclosed structures containing RNAs, proteins, lipids, metabolites, and other molecules, secreted by various cells into physiological fluids. EV-mediated transfer of biomolecules is a critical component variety pathological processes. Potential applications EVs in novel diagnostic therapeutic strategies have brought increasing attention. However, EV research remains highly challenging due to the inherently complex biogenesis their vast heterogeneity size, composition, origin. There need for establishment standardized methods that address sources pre-analytical analytical variability studies. Here, we review technologies developed isolation characterization discuss paths toward standardization research.

Language: Английский

Citations

369
Extracellular vesicles and nanoparticles: emerging complexities DOI Creative Commons
Dennis K. Jeppesen, Qin Zhang, Jeffrey L. Franklin

et al.

Trends in Cell Biology, Journal Year: 2023, Volume and Issue: 33(8), P. 667 - 681

Published: Feb. 1, 2023

The study of extracellular vesicles (EVs) and nanoparticles (NPs) is rapidly expanding because recent discoveries have revealed a much greater complexity diversity than was appreciated only few years ago. New types EVs NPs recently been described. Proteins nucleic acids previously thought to be packaged in exosomes appear more enriched different two identified amembranous NPs, exomeres supermeres. Thus, our understanding the cell biology intercellular communication facilitated by release state flux. In this review, we describe highlight advances, present major outstanding questions.

Language: Английский

Citations

368
Modern isolation and separation techniques for extracellular vesicles DOI Creative Commons
Thanaporn Liangsupree, Evgen Multia, Marja‐Liisa Riekkola

et al.

Journal of Chromatography A, Journal Year: 2020, Volume and Issue: 1636, P. 461773 - 461773

Published: Dec. 3, 2020

Extracellular vesicles (EVs) are heterogenous membrane-bound released from various origins. EVs play a crucial role in cellular communication and mediate several physiological pathological processes, highlighting their potential therapeutic diagnostic applications. Due to the rapid increase interests needs elucidate EV properties functions, numerous isolation separation approaches for have been developed overcome limitations of conventional techniques, such as ultracentrifugation. This review focuses on recently emerging modern including size-, charge-, affinity-based techniques while excluding ultracentrifugation precipitation-based due multiple limitations. The advantages drawbacks each technique discussed together with insights into Emerging all share similar features terms being time-effective, easy-to-operate, capable providing suitable desirable purity integrity applications interest. Combination hyphenation used yield best quality. most recent development using an automated on-line system selective trapping unit asymmetrical flow field-flow fractionation allows reliable subpopulations human plasma.

Language: Английский

Citations

360
Extracellular vesicle-based drug delivery systems for cancer treatment DOI Creative Commons
Sierra A. Walker, Sara Busatto, Anthony Pham

et al.

Theranostics, Journal Year: 2019, Volume and Issue: 9(26), P. 8001 - 8017

Published: Jan. 1, 2019

Extracellular vesicles (EVs) are naturally occurring cell-secreted nanoparticles that play important roles in many physiological and pathological processes. EVs enable intercellular communication by serving as delivery vehicles for a wide range of endogenous cargo molecules, such RNAs, proteins, carbohydrates, lipids. have also been found to display tissue tropism mediated surface integrins glycans, making them promising drug applications. Various methods can be used load therapeutic agents into EVs, additional modification strategies employed prolong circulation improve targeting. This review gives an overview EV-based cancer therapy.

Language: Английский

Citations

352