Abstract
Extracellular vesicles (EVs) are tiny membrane vesicles containing detailed cellular information. Recently, researchers have been focusing on EVs due to their role in intercellular communication, and prognostic, diagnostic, and therapeutic usage in medical purposes. In this chapter, we summarize the available technologies for EV characterization and describe their limitations and potential. Moreover, we highlight the emerging technologies with their development.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Abbreviations
- AF4:
-
Asymmetric flow field-flow fractionation
- AFM:
-
Atomic force microscopy
- AKI:
-
Kidney injury
- CCD:
-
Coupling system
- cryo-EM:
-
Cryogenic electron microscopy
- CSF:
-
Cerebrospinal fluid
- DLS:
-
Dynamic light scattering
- DUC:
-
Differential ultracentrifugation
- EM:
-
Electron microscopy
- EVs:
-
Extracellular vesicles
- FC:
-
Flow cytometry
- FCS:
-
Fluorescence correlation spectroscopy
- FIC:
-
Fluorescence imaging system
- Fl-NTA:
-
Emitted fluorescence
- IFC:
-
Image flow cytometer
- LSPRi:
-
Localized SPR imaging
- LTRS:
-
Laser tweezers Raman spectroscopy
- MISEV:
-
Minimal information for studies of extracellular vesicles
- MSC:
-
Mesenchymal stem cell
- MVBs:
-
Multivesicular bodies
- NTA:
-
Nanoparticle tracking analysis
- PBS:
-
Phosphate-buffered saline
- PCR:
-
Polymerase chain reaction
- PCS:
-
Photon-correlation spectroscopy
- PEG:
-
Polyethylene glycol
- PMT:
-
Photomultiplier tube
- Sc-NTA:
-
Scattered light
- SEA:
-
Fluorescent microscopic analysis
- SEC:
-
Size-exclusion chromatography
- SEM:
-
Scanning electron microscopy
- SERS:
-
Surface enhanced Raman spectroscopy
- Sp-IRIS:
-
Single-particle IRIS
- SPR:
-
Surface plasmon resonance
- SPT:
-
Single-particle tracking
- TEM:
-
Transmission electron microscopy
- TRPS:
-
Tunable pulse resistive sensing
References
Aalberts M, van Dissel-Emiliani FM, van Adrichem NP et al (2012) Identification of distinct populations of prostasomes that differentially express prostate stem cell antigen, annexin A1, and GLIPR2 in humans. Biol Reprod 86:82
Akagi T, Kato K, Hanamura N, Kobayashi M, Ichiki T (2014) Evaluation of desialylation effect on zeta potential of extracellular vesicles secreted from human prostate cancer cells by on-chip microcapillary electrophoresis. Jpn J Appl Phys 53:06JL01
Akagi T, Kato K, Kobayashi M et al (2015) On-chip immunoelectrophoresis of extracellular vesicles released from human breast cancer cells. PLoS One:10
Akers JC, Ramakrishnan V, Nolan JP et al (2016) Comparative analysis of technologies for quantifying extracellular vesicles (EVs) in clinical cerebrospinal fluids (CSF). PLoS One 11:e0149866
Alderton GK (2012) Metastasis. Exosomes drive premetastatic niche formation. Nat Rev Cancer 12:447
Allison DP, Mortensen NP, Sullivan CJ, Doktycz MJ (2010) Atomic force microscopy of biological samples. Wiley Interdiscip Rev Nanomed Nanobiotechnol 2:618–634
Al-Nedawi K, Meehan B, Micallef J et al (2008) Intercellular transfer of the oncogenic receptor EGFRvIII by microvesicles derived from tumour cells. Nat Cell Biol 10:619–624
Andreola G, Rivoltini L, Castelli C et al (2002) Induction of lymphocyte apoptosis by tumor cell secretion of FasL-bearing microvesicles. J Exp Med 195:1303–1316
Argov N, Wachsmann-Hogiu S, Freeman SL et al (2008) Size-dependent lipid content in human milk fat globules. J Agric Food Chem 56:7446–7450
Arraud N, Gounou C, Turpin D, Brisson AR (2016) Fluorescence triggering: a general strategy for enumerating and phenotyping extracellular vesicles by flow cytometry. Cytometry A 89:184–195
Arslan F, Lai RC, Smeets MB et al (2013) Mesenchymal stem cell-derived exosomes increase ATP levels, decrease oxidative stress and activate PI3K/Akt pathway to enhance myocardial viability and prevent adverse remodeling after myocardial ischemia/reperfusion injury. Stem Cell Res 10:301–312
Au Yeung CL, Co NN, Tsuruga T et al (2016) Exosomal transfer of stroma-derived miR21 confers paclitaxel resistance in ovarian cancer cells through targeting APAF1. Nat Commun 7:11150
Ayers L, Kohler M, Harrison P et al (2011) Measurement of circulating cell-derived microparticles by flow cytometry: sources of variability within the assay. Thromb Res 127:370–377
Baddela VS, Nayan V, Rani P, Onteru SK, Singh D (2016) Physicochemical biomolecular insights into buffalo milk-derived nanovesicles. Appl Biochem Biotechnol 178:544–557
Bank IE, Timmers L, Gijsberts CM et al (2015) The diagnostic and prognostic potential of plasma extracellular vesicles for cardiovascular disease. Expert Rev Mol Diagn 15:1577–1588
Baran J, Baj-Krzyworzeka M, Weglarczyk K et al (2010) Circulating tumour-derived microvesicles in plasma of gastric cancer patients. Cancer Immunol Immunother 59:841–850
Batrakova EV, Kim MS (2015) Using exosomes, naturally-equipped nanocarriers, for drug delivery. J Control Release 219:396–405
Berne, B.J., Pecora, R. (2000) Dynamic light scattering: with applications to chemistry, biology, and physics: Courier Corporation
Biggs CN, Siddiqui KM, Al-Zahrani AA et al (2016) Prostate extracellular vesicles in patient plasma as a liquid biopsy platform for prostate cancer using nanoscale flow cytometry. Oncotarget 7:8839–8849
Bosch S, de Beaurepaire L, Allard M et al (2016) Trehalose prevents aggregation of exosomes and cryodamage. Sci Rep 6:36162
Bozzola JJ, Russell LD (1999) Electron microscopy: principles and techniques for biologists. Jones & Bartlett Learning, Burlington
Brisson AR, Tan S, Linares R, Gounou C, Arraud N (2017) Extracellular vesicles from activated platelets: a semiquantitative cryo-electron microscopy and immuno-gold labeling study. Platelets 28:263–271
Bruno S, Grange C, Deregibus MC et al (2009) Mesenchymal stem cell-derived microvesicles protect against acute tubular injury. J Am Soc Nephrol 20:1053–1067
Bumbrah GS, Sharma RM (2016) Raman spectroscopy–basic principle, instrumentation and selected applications for the characterization of drugs of abuse. Egypt J Forensic Sci 6:209–215
Buschow SI, Nolte-‘t Hoen EN, van Niel G et al (2009) MHC II in dendritic cells is targeted to lysosomes or T cell-induced exosomes via distinct multivesicular body pathways. Traffic 10:1528–1542
Buzhynskyy N, Golczak M, Lai-Kee-Him J et al (2009) Annexin-A6 presents two modes of association with phospholipid membranes. A combined QCM-D, AFM and cryo-TEM study. J Struct Biol 168:107–116
Caby MP, Lankar D, Vincendeau-Scherrer C, Raposo G, Bonnerot C (2005) Exosomal-like vesicles are present in human blood plasma. Int Immunol 17:879–887
Carnell-Morris P, Tannetta D, Siupa A, Hole P, Dragovic R (2017) Analysis of extracellular vesicles using fluorescence nanoparticle tracking analysis. Methods Mol Biol 1660:153–173
Carney RP, Hazari S, Colquhoun M et al (2017) Multispectral optical tweezers for biochemical fingerprinting of CD9-positive exosome subpopulations. Anal Chem 89:5357–5363
Casado S, Lobo M, Paino CL (2017) Dynamics of plasma membrane surface related to the release of extracellular vesicles by mesenchymal stem cells in culture. Sci Rep 7:6767
Chandler WL (2016) Measurement of microvesicle levels in human blood using flow cytometry. Cytometry B Clin Cytom 90:326–336
Chandler WL, Yeung W, Tait JF (2011) A new microparticle size calibration standard for use in measuring smaller microparticles using a new flow cytometer. J Thromb Haemost 9:1216–1224
Chargaff E, West R (1946) The biological significance of the thromboplastic protein of blood. J Biol Chem 166:189–197
Charoenviriyakul C, Takahashi Y, Morishita M, Nishikawa M, Takakura Y (2018) Role of extracellular vesicle surface proteins in the pharmacokinetics of extracellular vesicles. Mol Pharm 15:1073–1080
Chen WW, Balaj L, Liau LM et al (2013) BEAMing and droplet digital PCR analysis of mutant IDH1 mRNA in glioma patient serum and cerebrospinal fluid extracellular vesicles. Mol Ther Nucleic Acids 2:e109
Choi DS (2015) Urinary extracellular vesicles for biomarker source to monitor polycystic kidney disease. Proteomics Clin Appl 9:447–448
Cizmar P, Yuana Y (2017) Detection and characterization of extracellular vesicles by transmission and cryo-transmission electron microscopy. Methods Mol Biol 1660:221–232
Colombo M, Raposo G, Thery C (2014) Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annu Rev Cell Dev Biol 30:255–289
Costa-Silva B, Aiello NM, Ocean AJ et al (2015) Pancreatic cancer exosomes initiate pre-metastatic niche formation in the liver. Nat Cell Biol 17:816–826
Crivelli B, Chlapanidas T, Perteghella S et al (2017) Mesenchymal stem/stromal cell extracellular vesicles: from active principle to next generation drug delivery system. J Control Release 262:104–117
Cvjetkovic A, Jang SC, Konecna B et al (2016) Detailed analysis of protein topology of extracellular vesicles-evidence of unconventional membrane protein orientation. Sci Rep 6:36338
Daaboul GG, Gagni P, Benussi L et al (2016) Digital detection of exosomes by interferometric imaging. Sci Rep 6:37246
Davies RT, Kim J, Jang SC et al (2012) Microfluidic filtration system to isolate extracellular vesicles from blood. Lab Chip 12:5202–5210
Day JS, Edwards HG, Dobrowski SA, Voice AM (2004) The detection of drugs of abuse in fingerprints using Raman spectroscopy II: cyanoacrylate-fumed fingerprints. Spectrochim Acta A Mol Biomol Spectrosc 60:1725–1730
De Broe ME, Wieme RJ, Logghe GN, Roels F (1977) Spontaneous shedding of plasma membrane fragments by human cells in vivo and in vitro. Clin Chim Acta 81:237–245
De Oliveira MA, Smith ZJ, Knorr F, De Araujo RE, Wachsmann-Hogiu S (2014) Long term Raman spectral study of power-dependent photodamage in red blood cells. Appl Phys Lett 104:103702
Deschout H, Raemdonck K, Stremersch S et al (2014) On-chip light sheet illumination enables diagnostic size and concentration measurements of membrane vesicles in biofluids. Nanoscale 6:1741–1747
Dragovic RA, Gardiner C, Brooks AS et al (2011) Sizing and phenotyping of cellular vesicles using Nanoparticle Tracking Analysis. Nanomedicine 7:780–788
Duijvesz D, Luider T, Bangma CH, Jenster G (2011) Exosomes as biomarker treasure chests for prostate cancer. Eur Urol 59:823–831
Erdbrugger U, Rudy CK, Etter ME et al (2014) Imaging flow cytometry elucidates limitations of microparticle analysis by conventional flow cytometry. Cytometry A 85:756–770
Ertsgaard CT, Wittenberg NJ, Klemme DJ et al (2018) Integrated nanogap platform for sub-volt dielectrophoretic trapping and real-time Raman imaging of biological nanoparticles. Nano Lett 18:5946–5953
Friedrich R, Block S, Alizadehheidari M et al (2017) A nano flow cytometer for single lipid vesicle analysis. Lab Chip 17:830–841
Gardiner C, Shaw M, Hole P et al (2014) Measurement of refractive index by nanoparticle tracking analysis reveals heterogeneity in extracellular vesicles. J Extracell Vesicles 3:25361
Gardiner C, Di Vizio D, Sahoo S et al (2016) Techniques used for the isolation and characterization of extracellular vesicles: results of a worldwide survey. J Extracell Vesicles 5:32945
Gigault J, Pettibone JM, Schmitt C, Hackley VA (2014) Rational strategy for characterization of nanoscale particles by asymmetric-flow field flow fractionation: a tutorial. Anal Chim Acta 809:9–24
Gustafsson J, Arvidson G, Karlsson G, Almgren M (1995) Complexes between cationic liposomes and DNA visualized by cryo-TEM. Biochim Biophys Acta 1235:305–312
Haka AS, Shafer-Peltier KE, Fitzmaurice M et al (2005) Diagnosing breast cancer by using Raman spectroscopy. Proc Natl Acad Sci 102:12371–12376
Hardij J, Cecchet F, Berquand A et al (2013) Characterisation of tissue factor-bearing extracellular vesicles with AFM: comparison of air-tapping-mode AFM and liquid Peak Force AFM. J Extracell Vesicles 2
Harding C, Heuser J, Stahl P (1983) Receptor-mediated endocytosis of transferrin and recycling of the transferrin receptor in rat reticulocytes. J Cell Biol 97:329–339
He M, Crow J, Roth M, Zeng Y, Godwin AK (2014) Integrated immunoisolation and protein analysis of circulating exosomes using microfluidic technology. Lab Chip 14:3773–3780
Hoog JL, Lotvall J (2015) Diversity of extracellular vesicles in human ejaculates revealed by cryo-electron microscopy. J Extracell Vesicles 4:28680
Huber V, Fais S, Iero M et al (2005) Human colorectal cancer cells induce T-cell death through release of proapoptotic microvesicles: role in immune escape. Gastroenterology 128:1796–1804
Im H, Yang K, Lee H, Castro CM (2017) Characterization of extracellular vesicles by surface plasmon resonance. Methods Mol Biol 1660:133–141
Issman L, Brenner B, Talmon Y, Aharon A (2013) Cryogenic transmission electron microscopy nanostructural study of shed microparticles. PLoS One 8:e83680
Jiang Y, Shi M, Liu Y et al (2017) Aptamer/AuNP biosensor for colorimetric profiling of exosomal proteins. Angew Chem Int Ed Engl 56:11916–11920
Kanwar SS, Dunlay CJ, Simeone DM, Nagrath S (2014) Microfluidic device (ExoChip) for on-chip isolation, quantification and characterization of circulating exosomes. Lab Chip 14:1891–1900
Kim HK, Song KS, Park YS et al (2003) Elevated levels of circulating platelet microparticles, VEGF, IL-6 and RANTES in patients with gastric cancer: possible role of a metastasis predictor. Eur J Cancer 39:184–191
Kim SH, Lechman ER, Bianco N et al (2005) Exosomes derived from IL-10-treated dendritic cells can suppress inflammation and collagen-induced arthritis. J Immunol 174:6440–6448
Kwizera EA, O'Connor R, Vinduska V et al (2018) Molecular detection and analysis of exosomes using surface-enhanced Raman scattering gold nanorods and a miniaturized device. Theranostics 8:2722–2738
Lamparski HG, Metha-Damani A, Yao JY et al (2002) Production and characterization of clinical grade exosomes derived from dendritic cells. J Immunol Methods 270:211–226
Leca J, Martinez S, Lac S et al (2016) Cancer-associated fibroblast-derived annexin A6+ extracellular vesicles support pancreatic cancer aggressiveness. J Clin Invest 126:4140–4156
Lee K, Fraser K, Ghaddar B et al (2018) Multiplexed profiling of single extracellular vesicles. ACS Nano 12:494–503
Libregts S, Arkesteijn GJA, Nemeth A, Nolte-'t Hoen ENM, Wauben MHM (2018) Flow cytometric analysis of extracellular vesicle subsets in plasma: impact of swarm by particles of non-interest. J Thromb Haemost 16:1423–1436
Liga A, Vliegenthart AD, Oosthuyzen W, Dear JW, Kersaudy-Kerhoas M (2015) Exosome isolation: a microfluidic road-map. Lab Chip 15:2388–2394
Linares R, Tan S, Gounou C, Brisson AR (2017) Imaging and quantification of extracellular vesicles by transmission electron microscopy. Methods Mol Biol 1545:43–54
Logozzi M, De Milito A, Lugini L et al (2009) High levels of exosomes expressing CD63 and caveolin-1 in plasma of melanoma patients. PLoS One 4:e5219
Lozano-Ramos I, Bancu I, Oliveira-Tercero A et al (2015) Size-exclusion chromatography-based enrichment of extracellular vesicles from urine samples. J Extracell Vesicles 4:27369
Luga V, Zhang L, Viloria-Petit AM et al (2012) Exosomes mediate stromal mobilization of autocrine Wnt-PCP signaling in breast cancer cell migration. Cell 151:1542–1556
Maas SL, Broekman ML, de Vrij J (2017) Tunable resistive pulse sensing for the characterization of extracellular vesicles. Methods Mol Biol 1545:21–33
Mateescu B, Kowal EJ, van Balkom BW et al (2017) Obstacles and opportunities in the functional analysis of extracellular vesicle RNA - an ISEV position paper. J Extracell Vesicles 6:1286095
Mathivanan S, Simpson RJ (2009) ExoCarta: a compendium of exosomal proteins and RNA. Proteomics 9:4997–5000
McNicholas K, Li JY, Michael MZ, Gleadle JM (2017) Albuminuria is not associated with elevated urinary vesicle concentration but can confound nanoparticle tracking analysis. Nephrology 22:854–863
van der Meel R, Fens MH, Vader P et al (2014) Extracellular vesicles as drug delivery systems: lessons from the liposome field. J Control Release 195:72–85
Merchant ML, Rood IM, Deegens JKJ, Klein JB (2017) Isolation and characterization of urinary extracellular vesicles: implications for biomarker discovery. Nat Rev Nephrol 13:731–749
Moon PG, Lee JE, Cho YE et al (2016) Identification of developmental endothelial locus-1 on circulating extracellular vesicles as a novel biomarker for early breast cancer detection. Clin Cancer Res 22:1757–1766
Mork M, Pedersen S, Botha J, Lund SM, Kristensen SR (2016) Preanalytical, analytical, and biological variation of blood plasma submicron particle levels measured with nanoparticle tracking analysis and tunable resistive pulse sensing. Scand J Clin Lab Invest 76:349–360
Nanou A, Crespo M, Flohr P, De Bono JS, Terstappen L (2018) Scanning electron microscopy of circulating tumor cells and tumor-derived extracellular vesicles. Cancers (Basel) 10:416
Nolan JP, Duggan E (2018) Analysis of individual extracellular vesicles by flow cytometry. Methods Mol Biol 1678:79–92
Nolan JP, Jones JC (2017) Detection of platelet vesicles by flow cytometry. Platelets 28:256–262
Palma J, Yaddanapudi SC, Pigati L et al (2012) MicroRNAs are exported from malignant cells in customized particles. Nucleic Acids Res 40:9125–9138
Park J, Hwang M, Choi B et al (2017) Exosome classification by pattern analysis of surface-enhanced Raman spectroscopy data for lung cancer diagnosis. Anal Chem 89:6695–6701
Pearson LJ, Klaharn I-Y, Thongsawang B et al (2017) Multiple extracellular vesicle types in peritoneal dialysis effluent are prominent and contain known biomarkers. PLoS One 12:e0178601
Peinado H, Aleckovic M, Lavotshkin S et al (2012) Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET. Nat Med 18:883–891
van der Pol E, van Gemert MJ, Sturk A, Nieuwland R, van Leeuwen TG (2012) Single vs. swarm detection of microparticles and exosomes by flow cytometry. J Thromb Haemost 10:919–930
van der Pol E, Sturk A, van Leeuwen T, Nieuwland R, Coumans F (2018) Standardization of extracellular vesicle measurements by flow cytometry through vesicle diameter approximation. J Thromb Haemost 16:1236–1245
Pospichalova V, Svoboda J, Dave Z et al (2015) Simplified protocol for flow cytometry analysis of fluorescently labeled exosomes and microvesicles using dedicated flow cytometer. J Extracell Vesicles 4:25530
Puppels GJ, de Mul FF, Otto C et al (1990) Studying single living cells and chromosomes by confocal Raman microspectroscopy. Nature 347:301–303
Qian H, Sheetz MP, Elson EL (1991) Single particle tracking. Analysis of diffusion and flow in two-dimensional systems. Biophys J 60:910–921
Quek C, Hill AF (2017) The role of extracellular vesicles in neurodegenerative diseases. Biochem Biophys Res Commun 483:1178–1186
Raghu D, Christodoulides JA, Christophersen M et al (2018) Nanoplasmonic pillars engineered for single exosome detection. PLoS One 13:e0202773
Raposo G, Stoorvogel W (2013) Extracellular vesicles: exosomes, microvesicles, and friends. J Cell Biol 200:373–383
Raposo G, Nijman HW, Stoorvogel W et al (1996) B lymphocytes secrete antigen-presenting vesicles. J Exp Med 183:1161–1172
Richards KE, Zeleniak AE, Fishel ML et al (2017) Cancer-associated fibroblast exosomes regulate survival and proliferation of pancreatic cancer cells. Oncogene 36:1770–1778
Saveyn H, De Baets B, Thas O et al (2010) Accurate particle size distribution determination by nanoparticle tracking analysis based on 2-D Brownian dynamics simulation. J Colloid Interface Sci 352:593–600
Settle FA (1997) Handbook of instrumental techniques for analytical chemistry: prentice Hall PTR
Skog J, Wurdinger T, van Rijn S et al (2008) Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol 10:1470–1476
Smith ZJ, Lee C, Rojalin T et al (2015) Single exosome study reveals subpopulations distributed among cell lines with variability related to membrane content. J Extracell Vesicles 4:28533
Sokolova V, Ludwig AK, Hornung S et al (2011) Characterisation of exosomes derived from human cells by nanoparticle tracking analysis and scanning electron microscopy. Colloids Surf B Biointerfaces 87:146–150
Somasundaram R, Herlyn M (2012) Melanoma exosomes: messengers of metastasis. Nat Med 18:853–854
Stoner SA, Duggan E, Condello D et al (2016) High sensitivity flow cytometry of membrane vesicles. Cytometry A 89:196–206
Suárez H, Gámez-Valero A, Reyes R et al (2017) A bead-assisted flow cytometry method for the semi-quantitative analysis of extracellular vesicles. Sci Rep 7:11271–11271
Szajnik M, Derbis M, Lach M et al (2013) Exosomes in plasma of patients with ovarian carcinoma: potential biomarkers of tumor progression and response to therapy. Gynecol Obstet (Sunnyvale)
Tauro BJ, Greening DW, Mathias RA et al (2012) Comparison of ultracentrifugation, density gradient separation, and immunoaffinity capture methods for isolating human colon cancer cell line LIM1863-derived exosomes. Methods 56:293–304
Taylor DD, Shah S (2015) Methods of isolating extracellular vesicles impact down-stream analyses of their cargoes. Methods 87:3–10
Tchanque-Fossuo CN, Gong B, Poushanchi B et al (2013) Raman spectroscopy demonstrates Amifostine induced preservation of bone mineralization patterns in the irradiated murine mandible. Bone 52:712–717
Thakur A, Qiu G, Ng SP et al (2017) Direct detection of two different tumor-derived extracellular vesicles by SAM-AuNIs LSPR biosensor. Biosens Bioelectron 94:400–407
Thery C, Amigorena S, Raposo G, Clayton A (2006) Isolation and characterization of exosomes from cell culture supernatants and biological fluids. Curr Protoc Cell Biol Chapter 3:Unit 3.22
Thery C, Witwer KW, Aikawa E et al (2018) 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. J Extracell Vesicles 7:1535750
Thompson RF, Walker M, Siebert CA, Muench SP, Ranson NA (2016) An introduction to sample preparation and imaging by cryo-electron microscopy for structural biology. Methods 100:3–15
Tian YF, Ning CF, He F, Yin BC, Ye BC (2018) Highly sensitive detection of exosomes by SERS using gold nanostar@Raman reporter@nanoshell structures modified with a bivalent cholesterol-labeled DNA anchor. Analyst 143:4915–4922
Torregrosa Paredes P, Gutzeit C, Johansson S et al (2014) Differences in exosome populations in human breast milk in relation to allergic sensitization and lifestyle. Allergy 69:463–471
Usman WM, Pham TC, Kwok YY et al (2018) Efficient RNA drug delivery using red blood cell extracellular vesicles. Nat Commun 9:2359
Valadi H, Ekstrom K, Bossios A et al (2007) Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 9:654–659
Vestad B, Llorente A, Neurauter A et al (2017) Size and concentration analyses of extracellular vesicles by nanoparticle tracking analysis: a variation study. J Extracell Vesicles 6:1344087
van der Vlist EJ, Nolte-'t Hoen EN, Stoorvogel W, Arkesteijn GJ, Wauben MH (2012) Fluorescent labeling of nano-sized vesicles released by cells and subsequent quantitative and qualitative analysis by high-resolution flow cytometry. Nat Protoc 7:1311–1326
Vogel R, Coumans FA, Maltesen RG et al (2016) A standardized method to determine the concentration of extracellular vesicles using tunable resistive pulse sensing. J Extracell Vesicles 5:31242
Vogel R, Pal AK, Jambhrunkar S et al (2017) High-resolution single particle zeta potential characterisation of biological nanoparticles using tunable resistive pulse sensing. Sci Rep 7:17479
Vorselen D, Marchetti M, Lopez-Iglesias C et al (2018a) Multilamellar nanovesicles show distinct mechanical properties depending on their degree of lamellarity. Nanoscale 10:5318–5324
Vorselen D, van Dommelen SM, Sorkin R et al (2018b) The fluid membrane determines mechanics of erythrocyte extracellular vesicles and is softened in hereditary spherocytosis. Nat Commun 9:4960
Wahlgren J, De LKT, Brisslert M et al (2012) Plasma exosomes can deliver exogenous short interfering RNA to monocytes and lymphocytes. Nucleic Acids Res 40:e130
Wang Z, Wu HJ, Fine D et al (2013) Ciliated micropillars for the microfluidic-based isolation of nanoscale lipid vesicles. Lab Chip 13:2879–2882
Wang Z, Zong S, Wang Y et al (2018) Screening and multiple detection of cancer exosomes using an SERS-based method. Nanoscale 10:9053–9062
Weatherall E, Willmott GR (2015) Applications of tunable resistive pulse sensing. Analyst 140:3318–3334
Welker MW, Reichert D, Susser S et al (2012) Soluble serum CD81 is elevated in patients with chronic hepatitis C and correlates with alanine aminotransferase serum activity. PLoS One 7:e30796
Wolf P (1967) The nature and significance of platelet products in human plasma. Br J Haematol 13:269–288
Wu K, Xing F, Wu SY, Watabe K (2017) Extracellular vesicles as emerging targets in cancer: recent development from bench to bedside. Biochim Biophys Acta Rev Cancer 1868:538–563
Wyss R, Grasso L, Wolf C et al (2014) Molecular and dimensional profiling of highly purified extracellular vesicles by fluorescence fluctuation spectroscopy. Anal Chem 86:7229–7233
Yamashita T, Takahashi Y, Nishikawa M, Takakura Y (2016) Effect of exosome isolation methods on physicochemical properties of exosomes and clearance of exosomes from the blood circulation. Eur J Pharm Biopharm 98:1–8
Yan Z, Dutta S, Liu Z et al (2019) A label-free platform for identification of exosomes from different sources. ACS Sens 4:488–497
Yang J, Wei F, Schafer C, Wong DT (2014) Detection of tumor cell-specific mRNA and protein in exosome-like microvesicles from blood and saliva. PLoS One 9:e110641
Zhang W, Peng P, Kuang Y et al (2016) Characterization of exosomes derived from ovarian cancer cells and normal ovarian epithelial cells by nanoparticle tracking analysis. Tumor Biol 37:4213–4221
Acknowledgments
We would like to thank the Deanship of Faculty of Veterinary Medicine at Damanhour University for their technical support.
This article does not contain any studies with animals performed by any of the authors.
This article does not contain any studies with human participants performed by any of the authors.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2021 Springer Nature Singapore Pte Ltd.
About this chapter
Cite this chapter
Noreldin, A.E., Khafaga, A.F., Barakat, R.A. (2021). Isolation and Characterization of Extracellular Vesicles: Classical and Modern Approaches. In: Alzahrani, F.A., Saadeldin, I.M. (eds) Role of Exosomes in Biological Communication Systems. Springer, Singapore. https://doi.org/10.1007/978-981-15-6599-1_1
Download citation
DOI: https://doi.org/10.1007/978-981-15-6599-1_1
Published:
Publisher Name: Springer, Singapore
Print ISBN: 978-981-15-6598-4
Online ISBN: 978-981-15-6599-1
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)