Challenges and opportunities in the study of extracellular vesicles: Global institutional context and national state of the art

Susana Novoa-Herrán, .

Keywords: Extracellular Vesicles, Exosomes, Cell-Derived Microparticles, chemical phenomenal, chemistry techniques, analytical, terminology as topic, resource guide.

Abstract

In the last decade, the number of studies and publications on extracellular vesicles (EV) and exosomes has boomed. Colombia has displayed interest and progress in their study as shown in the increase of research project publications and products. However, this research field is still developing and has its own analytical challenges and technical limitations. For planning research projects and developing EV studies it is necessary to consider what is the state of the scientific field worldwide concerning EV nomenclature and classification, available techniques, resources, requirements and quality specifications, and the institutions that regulate the field. Answering this question will elicit EV studies that comply with international standards and respond to institutional demands and recommendations.
However, the scientific information available is scattered and not all the aspects are considered in full.
In this update, the available information is condensed and the official terms and currently defined nomenclature is presented, as well as the evolution of the field, the homogenization of the experimental parameters, the establishment of scientific authorities, institutions, and resources, and the recommendations generated worldwide for their development and research including their isolation, characterization, and functional studies. Finally, I analyzed the national context in a critical way, considering institutional strengths, common mistakes, and available analytical techniques and technologies.

Downloads

Download data is not yet available.

References

Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P. General principles of cell communication. Mol Biol Cell. 4th ed. New York: Garland Science; 2002.

Jones SM, Kazlauskas A. Growth Factor-Dependent Signaling and Cell Cycle Progression. Chem Rev. 2001;101(8):2413-24.

O'Shea JJ, Gadina M, Siegel RM. 9 - Cytokines and Cytokine Receptors. In: Rich RR, Fleisher TA, Shearer WT, Schroeder HW, Frew AJ, Weyand CM, editors. Clinical Immunology (Fifth Edition). London: Content Repository Only!; 2019. p. 127-55.e1.

Lauder JM. Neurotransmitters as growth regulatory signals: role of receptors and second messengers. Trends Neurosci. 1993;16(6):233-40.

Meldolesi J. Exosomes and Ectosomes in Intercellular Communication. Curr Biol. 2018;28(8):R435-R44.

Mittelbrunn M, Sánchez-Madrid F. Intercellular communication: diverse structures for exchange of genetic information. Nat Rev Mol Cell Biol. 2012;13(5):328-35.

Lötvall J, Hill AF, Hochberg F, Buzás EI, Di Vizio D, Gardiner C, et al. Minimal experimental requirements for definition of extracellular vesicles and their functions: a position statement from the International Society for Extracellular Vesicles. Journal of Extracellular Vesicles. 2014;3(1):26913.

Van Deun J, Mestdagh P, Agostinis P, Akay Ö, Anand S, Anckaert J, et al. EV-TRACK: transparent reporting and centralizing knowledge in extracellular vesicle research. Nat Methods. 2017;14(3):228-32.

Aaronson S, Behrens U, Orner R, Haines TH. Ultrastructure of intracellular and extracellular vesicles, membranes, and myelin figures produced by Ochromonas danica. J Ultrastruct Res. 1971;35(5):418-30.

Théry C, Witwer KW, Aikawa E, Alcaraz MJ, Anderson JD, Andriantsitohaina R, et al. 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. Journal of Extracellular Vesicles. 2018;7(1):1535750.

Stegmayr B, Ronquist G. Promotive effect on human sperm progressive motility by prostasomes. Urol Res. 1982;10(5):253-7.

Minciacchi VR, You S, Spinelli C, Morley S, Zandian M, Aspuria P-J, et al. Large oncosomes contain distinct protein cargo and represent a separate functional class of tumor-derived extracellular vesicles. Oncotarget. 2015;6(13).

Anderson HC. VESICLES ASSOCIATED WITH CALCIFICATION IN THE MATRIX OF EPIPHYSEAL CARTILAGE. The Journal of Cell Biology. 1969;41(1):59-72.

Raposo G, Stoorvogel W. Extracellular vesicles: Exosomes, microvesicles, and friends. The Journal of Cell Biology. 2013;200(4):373-83.

Trams EG, Lauter CJ, Norman Salem, Jr., Heine U. Exfoliation of membrane ecto-enzymes in the form of micro-vesicles. Biochimica et Biophysica Acta (BBA) - Biomembranes. 1981;645(1):63-70.

Harding C, Heuser J, Stahl P. Receptor-mediated endocytosis of transferrin and recycling of the transferrin receptor in rat reticulocytes. The Journal of Cell Biology. 1983;97(2):329-39.

Pan B-T, Johnstone RM. Fate of the transferrin receptor during maturation of sheep reticulocytes in vitro: Selective externalization of the receptor. Cell. 1983;33(3):967-78.

Raposo G, Nijman HW, Stoorvogel W, Liejendekker R, Harding CV, Melief CJ, et al. B lymphocytes secrete antigen-presenting vesicles. The Journal of Experimental Medicine. 1996;183(3):1161-72.

Zitvogel L, Regnault A, Lozier A, Wolfers J, Flament C, Tenza D, et al. Eradication of established murine tumors using a novel cell-free vaccine: dendritic cell derived exosomes. Nat Med. 1998;4(5):594-600.

Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, et al. Gene Ontology: tool for the unification of biology. Nat Genet. 2000;25(1):25-9.

The Gene Ontology Consortium. The Gene Ontology Resource: 20 years and still GOing strong. Nucleic Acids Res. 2019;47(D1):D330-D8.

Medical Subject Headings: MeSH Bethesda, MD: NIH - NLM; 2019 [2019:[Available from: https://meshb.nlm.nih.gov/search.

Descriptores en Ciencias de la Salud: DeCS [Internet]. Sao Paulo (SP): BIREME / OPS / OMS; 2019 [updated 6/2019citado 22/11/2019]. 2019:[Available from: http://decs.bvsalud.org/E/homepagee.htm.

Cocucci E, Meldolesi J. Ectosomes and exosomes: shedding the confusion between extracellular vesicles. Trends Cell Biol. 2015;25(6):364-72.

Cheung K-H, Keerthikumar S, Roncaglia P, Subramanian SL, Roth ME, Samuel M, et al. Extending gene ontology in the context of extracellular RNA and vesicle communication. Journal of Biomedical Semantics. 2016;7(1):19.

György B, Szabó TG, Pásztói M, Pál Z, Misják P, Aradi B, et al. Membrane vesicles, current state-of-the-art: emerging role of extracellular vesicles. Cellular And Molecular Life Sciences: CMLS. 2011;68(16):2667-88.

Thery C, Ostrowski M, Segura E. Membrane vesicles as conveyors of immune responses. Nature Reviews Immunology. 2009;9(8):581-93.

Lötvall J, Rajendran L, Gho Y-S, Thery C, Wauben M, Raposo G, et al. The launch of Journal of Extracellular Vesicles (JEV), the official journal of the International Society for Extracellular Vesicles – about microvesicles, exosomes, ectosomes and other extracellular vesicles. Journal of Extracellular Vesicles. 2012;1(1):18514.

Gould SJ, Taylor D, Chiesi A, Kuo WP. Announcing Exosomes and Microvesicles, the Official Journal of the American Society for Exosomes and Microvesicles. Exosomes and Microvesicles. 2013;1:1.

ISEV RNA Workshop—New York City, October 1–2, 2012. Journal of Extracellular Vesicles. 2012;1(1):19857.

Hill AF, Pegtel DM, Lambertz U, Leonardi T, O'Driscoll L, Pluchino S, et al. ISEV position paper: extracellular vesicle RNA analysis and bioinformatics. Journal of Extracellular Vesicles. 2013;2(1):22859.

Witwer KW, Buzás EI, Bemis LT, Bora A, Lässer C, Lötvall J, et al. Standardization of sample collection, isolation and analysis methods in extracellular vesicle research. Journal of Extracellular Vesicles. 2013;2:1-25.

Gardiner C, Vizio DD, Sahoo S, Théry C, Witwer KW, Wauben M, et al. Techniques used for the isolation and characterization of extracellular vesicles: results of a worldwide survey. Journal of Extracellular Vesicles. 2016;5(1):32945.

Van Deun J, Hendrix A. Is your article EV-TRACKed? Journal of Extracellular Vesicles. 2017;6(1):1379835.

Kim D-K, Kang B, Kim OY, Choi D-s, Lee J, Kim SR, et al. EVpedia: an integrated database of high-throughput data for systemic analyses of extracellular vesicles. Journal of Extracellular Vesicles. 2013.

Kim D-K, Lee J, Kim SR, Choi D-S, Yoon YJ, Kim JH, et al. EVpedia: a community web portal for extracellular vesicles research. Bioinformatics. 2015;31(6):933-9.

Simpson RJ, Kalra H, Mathivanan S. ExoCarta as a resource for exosomal research. Journal of Extracellular Vesicles. 2012;1(1):18374.

Keerthikumar S, Chisanga D, Ariyaratne D, Al Saffar H, Anand S, Zhao K, et al. ExoCarta: A Web-Based Compendium of Exosomal Cargo. J Mol Biol. 2016;428(4):688-92.

Kalra H, Simpson RJ, Ji H, Aikawa E, Altevogt P, Askenase P, et al. Vesiclepedia: A Compendium for Extracellular Vesicles with Continuous Community Annotation. PLoS Biol. 2012;10(12):e1001450.

Pathan M, Fonseka P, Chitti SV, Kang T, Sanwlani R, Van Deun J, et al. Vesiclepedia 2019: a compendium of RNA, proteins, lipids and metabolites in extracellular vesicles. Nucleic Acids Res. 2019;47(D1):D516-D9.

Ainsztein AM, Brooks PJ, Dugan VG, Ganguly A, Guo M, Howcroft TK, et al. The NIH Extracellular RNA Communication Consortium. Journal of Extracellular Vesicles. 2015;4(1):27493.

Murillo OD, Thistlethwaite W, Rozowsky J, Subramanian SL, Lucero R, Shah N, et al. exRNA Atlas Analysis Reveals Distinct Extracellular RNA Cargo Types and Their Carriers Present across Human Biofluids. Cell. 2019;177(2):463-77.e15.

Liu T, Zhang Q, Zhang J, Li C, Miao Y-R, Lei Q, et al. EVmiRNA: a database of miRNA profiling in extracellular vesicles. Nucleic Acids Res. 2018;47(D1):D89-D93.

Pathan M, Keerthikumar S, Ang C-S, Gangoda L, Quek CYJ, Williamson NA, et al. FunRich: An open access standalone functional enrichment and interaction network analysis tool. Proteomics. 2015;15(15):2597-601.

Pathan M, Keerthikumar S, Chisanga D, Alessandro R, Ang C-S, Askenase P, et al. A novel community driven software for functional enrichment analysis of extracellular vesicles data. Journal of Extracellular Vesicles. 2017;6(1):1321455.

Lässer C, Théry C, Buzás EI, Mathivanan S, Zhao W, Gho YS, et al. The International Society for Extracellular Vesicles launches the first massive open online course on extracellular vesicles. Journal of Extracellular Vesicles. 2016;5(1):34299.

Taylor DD, Shah S. Methods of isolating extracellular vesicles impact down-stream analyses of their cargoes. Methods. 2015;87:3-10.

Bobrie A, Colombo M, Krumeich S, Raposo G, Théry C. Diverse subpopulations of vesicles secreted by different intracellular mechanisms are present in exosome preparations obtained by differential ultracentrifugation. Journal of Extracellular Vesicles. 2012;1(1):18397.

Théry C, Amigorena S, Raposo G, Clayton A. Isolation and characterization of exosomes from cell culture supernatants and biological fluids. Current Protocols in Cell Biology. 302006. p. 3.22.1-3..9.

Kowal J, Arras G, Colombo M, Jouve M, Morath JP, Primdal-Bengtson B, et al. Proteomic comparison defines novel markers to characterize heterogeneous populations of extracellular vesicle subtypes. Proc Natl Acad Sci U S A. 2016;113(8):E968-77.

Popovic M. Routine and novel methods for isolation of extracellular vesicles. Biologia Serbica. 2019;41(2):36-43.

Konoshenko MY, Lekchnov EA, Vlassov AV, Laktionov PP. Isolation of Extracellular Vesicles: General Methodologies and Latest Trends. BioMed research international. 2018;2018:8545347-.

Boriachek K, Islam MN, Möller A, Salomon C, Nguyen N-T, Hossain MSA, et al. Biological Functions and Current Advances in Isolation and Detection Strategies for Exosome Nanovesicles. Small. 2018;14(6):1702153.

Coumans FAW, Brisson AR, Buzas EI, Dignat-George F, Drees EEE, El-Andaloussi S, et al. Methodological Guidelines to Study Extracellular Vesicles. Circul Res. 2017;120(10):1632-48.

Szatanek R, Baj-Krzyworzeka M, Zimoch J, Lekka M, Siedlar M, Baran J. The Methods of Choice for Extracellular Vesicles (EVs) Characterization. International Journal of Molecular Sciences. 2017;18(6):1153.

Clayton A, Boilard E, Buzas EI, Cheng L, Falcón-Perez JM, Gardiner C, et al. Considerations towards a roadmap for collection, handling and storage of blood extracellular vesicles. Journal of Extracellular Vesicles. 2019;8(1):1647027.

Cvjetkovic A, Lötvall J, Lässer C. The influence of rotor type and centrifugation time on the yield and purity of extracellular vesicles. Journal of Extracellular Vesicles. 2014;3(1):23111.

Livshits MA, Khomyakova E, Evtushenko EG, Lazarev VN, Kulemin NA, Semina SE, et al. Isolation of exosomes by differential centrifugation: Theoretical analysis of a commonly used protocol. Scientific Reports. 2015;5(1):17319.

Yang JS, Lee JC, Byeon SK, Rha KH, Moon MH. Size Dependent Lipidomic Analysis of Urinary Exosomes from Patients with Prostate Cancer by Flow Field-Flow Fractionation and Nanoflow Liquid Chromatography-Tandem Mass Spectrometry. Anal Chem. 2017;89(4):2488-96.

Zhang H, Freitas D, Kim HS, Fabijanic K, Li Z, Chen H, et al. Identification of distinct nanoparticles and subsets of extracellular vesicles by asymmetric flow field-flow fractionation. Nat Cell Biol. 2018;20(3):332-43.

Kanwar SS, Dunlay CJ, Simeone DM, Nagrath S. Microfluidic device (ExoChip) for on-chip isolation, quantification and characterization of circulating exosomes. Lab Chip. 2014;14(11):1891-900.

Contreras-Naranjo JC, Wu H-J, Ugaz VM. Microfluidics for exosome isolation and analysis: enabling liquid biopsy for personalized medicine. Lab Chip. 2017;17(21):3558-77.

Koritzinsky EH, Street JM, Chari RR, Glispie DM, Bellomo TR, Aponte AM, et al. Circadian variation in the release of small extracellular vesicles can be normalized by vesicle number or TSG101. American Journal of Physiology-Renal Physiology. 2019;317(5):F1098-F110.

Mateescu B, Kowal EJK, van Balkom BWM, Bartel S, Bhattacharyya SN, Buzás EI, et al. Obstacles and opportunities in the functional analysis of extracellular vesicle RNA – an ISEV position paper. Journal of Extracellular Vesicles. 2017;6(1):1286095.

Mathieu M, Martin-Jaular L, Lavieu G, Théry C. Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell-to-cell communication. Nat Cell Biol. 2019;21(1):9-17.

Mulcahy LA, Pink RC, Carter DRF. Routes and mechanisms of extracellular vesicle uptake. Journal of Extracellular Vesicles. 2014;3(1):24641.

Gorabi AM, Kiaie N, Barreto GE, Read MI, Tafti HA, Sahebkar A. The Therapeutic Potential of Mesenchymal Stem Cell–Derived Exosomes in Treatment of Neurodegenerative Diseases. Mol Neurobiol. 2019;56(12):8157-67.

Burbano C, Rojas M, Vasquez G, Castano D. Microparticles That Form Immune Complexes as Modulatory Structures in Autoimmune Responses. Mediators Inflamm. 2015;2015:267590.

Burbano C, Villar-Vesga J, Orejuela J, Muñoz C, Vanegas A, Vásquez G, et al. Potential Involvement of Platelet-Derived Microparticles and Microparticles Forming Immune Complexes during Monocyte Activation in Patients with Systemic Lupus Erythematosus. Frontiers in Immunology. 2018;9(322).

Burbano C, Villar-Vesga J, Vásquez G, Muñoz-Vahos C, Rojas M, Castaño D. Proinflammatory Differentiation of Macrophages Through Microparticles That Form Immune Complexes Leads to T- and B-Cell Activation in Systemic Autoimmune Diseases. Frontiers in Immunology. 2019;10(2058).

Burbano C, Rojas M, Muñoz-Vahos C, Vanegas-García A, Correa LA, Vásquez G, et al. Extracellular vesicles are associated with the systemic inflammation of patients with seropositive rheumatoid arthritis. Scientific Reports. 2018;8(1):17917.

Atehortúa L, Rojas M, Vásquez G, Muñoz-Vahos CH, Vanegas-García A, Posada-Duque RA, et al. Endothelial activation and injury by microparticles in patients with systemic lupus erythematosus and rheumatoid arthritis. Arthrit Res Ther. 2019;21(1):34.

Bautista D, Rodríguez L-S, Franco MA, Angel J, Barreto A. Caco-2 cells infected with rotavirus release extracellular vesicles that express markers of apoptotic bodies and exosomes. Cell Stress Chaperones. 2015;20(4):697-708.

Tobón-Arroyave SI, Celis-Mejía N, Córdoba-Hidalgo MP, Isaza-Guzmán DM. Decreased salivary concentration of CD9 and CD81 exosome-related tetraspanins may be associated with the periodontal clinical status. J Clin Periodontol. 2019;46(4):470-80.

Roballo KCS, da Silveira JC, Bressan FF, de Souza AF, Pereira VM, Porras JEP, et al. Neurons-derived extracellular vesicles promote neural differentiation of ADSCs: a model to prevent peripheral nerve degeneration. Scientific Reports. 2019;9(1):11213.

Toda H, Diaz-Varela M, Segui-Barber J, Roobsoong W, Baro B, Garcia-Silva S, et al. Plasma-derived extracellular vesicles from Plasmodium vivax patients signal spleen fibroblasts via NF-kB facilitating parasite cytoadherence. Nature Communications. 2020;11(1):2761.

Prados-Rosales R, Carreno LJ, Batista-Gonzalez A, Baena A, Venkataswamy MM, Xu J, et al. Mycobacterial membrane vesicles administered systemically in mice induce a protective immune response to surface compartments of Mycobacterium tuberculosis. mBio. 2014;5(5):e01921-14.

Barreto A, Rodríguez L-S, Rojas OL, Wolf M, Greenberg HB, Franco MA, et al. Membrane Vesicles Released by Intestinal Epithelial Cells Infected with Rotavirus Inhibit T-Cell Function. Viral Immunol. 2010;23(6):595-608.

Gil-Bona A, Llama-Palacios A, Parra CM, Vivanco F, Nombela C, Monteoliva L, et al. Proteomics Unravels Extracellular Vesicles as Carriers of Classical Cytoplasmic Proteins in Candida albicans. J Proteome Res. 2015;14(1):142-53.

Ospina-Prieto S, Chaiwangyen W, Schleussner E, Markert UR, Morales-Prieto DM. Role of EMVs containing miR-141 in the intercellular communication of trophoblastic and immune cells. J Reprod Immunol. 2015;111:21-2.

de la Torre Gomez C, Goreham RV, Bech Serra JJ, Nann T, Kussmann M. "Exosomics"-A Review of Biophysics, Biology and Biochemistry of Exosomes With a Focus on Human Breast Milk. Front Genet. 2018;9:92-.

MinCiencias. Repositorio Principal CENDOC Bogotá2020 [Available from: http://repositorio.colciencias.gov.co/.

MinCiencias. Buscador Proyectos Bogotá2020 [updated Febrero 8, 2020. Available from: https://sba.minciencias.gov.co/Buscador_Proyectos/busqueda?q=&pagenum=1&start=0&type=load.

MinCiencias. Buscador Productos Bogotá2020 [updated Febrero 22, 2020. Available from: https://sba.minciencias.gov.co/Buscador_Productos/busqueda?q=&pagenum=1&start=0&type=load.

Roy S, Hochberg FH, Jones PS. Extracellular vesicles: the growth as diagnostics and therapeutics; a survey. Journal of extracellular vesicles. 2018;7(1):1438720-.

How to Cite
1.
Novoa-Herrán S. Challenges and opportunities in the study of extracellular vesicles: Global institutional context and national state of the art. biomedica [Internet]. 2021 Sep. 24 [cited 2024 May 19];41(3):555-89. Available from: https://revistabiomedica.org/index.php/biomedica/article/view/5749
Published
2021-09-24
Section
Update

Altmetric

Article metrics
Abstract views
Galley vies
PDF Views
HTML views
Other views
Crossref Cited-by logo
QR Code