Systematic characterization of extracellular vesicle sorting domains and quantification at the single molecule – single vesicle level by fluorescence correlation spectroscopy and single particle imaging

References

• Del Conde I, Shrimpton CN, Thiagarajan P, et al. Tissue-factor-bearing microvesicles arise from lipid rafts and fuse with activated platelets to initiate coagulation. Blood. 2005;106:1604–22.
   PubMed Web of Science ®Google Scholar
• Segura E, et al. ICAM-1 on exosomes from mature dendritic cells is critical for efficient naive T-cell priming. Blood. 2005;106:216–223.
   PubMed Web of Science ®Google Scholar
• Viaud S, et al. Dendritic cell-derived exosomes promote natural killer cell activation and proliferation: a role for NKG2D ligands and IL-15Ra. PLoS One. 2009;4:e4942.
   PubMed Web of Science ®Google Scholar
• Lai RC, et al. Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury. Stem Cell Res. 2010;4:214.
   PubMed Web of Science ®Google Scholar
• Camussi G, et al. Exosome/microvesicle-mediated epigenetic reprogramming of cells. Am J Cancer Res. 2011;1:98–110.
   PubMed Web of Science ®Google Scholar
• Gatti S, et al. Microvesicles derived from human adult mesenchymal stem cells protect against ischaemia-reperfusion-induced acute and chronic kidney injury. Nephrol Dial Transplant. 2011;26:1474–1483.
   PubMed Web of Science ®Google Scholar
• Melo SA, et al. Glypican-1 identifies cancer exosomes and detects early pancreatic cancer. Nature. 2015;523:177–182.
   PubMed Web of Science ®Google Scholar
• Matsumura T, et al. Exosomal microRNA in serum is a novel biomarker of recurrence in human colorectal cancer. Br J Cancer. 2015;113:275–281.
   PubMed Web of Science ®Google Scholar
• Michael A, et al. Exosomes from human saliva as a source of microRNA biomarkers. Oral Dis. 2010;16:34–38.
   PubMed Web of Science ®Google Scholar
• Cazzoli R, et al. MicroRNAs derived from circulating exosomes as noninvasive biomarkers for screening and diagnosing lung cancer. J Thorac Oncol. 2013;8:1156–1162.
   PubMed Web of Science ®Google Scholar
• Alvarez-Erviti L, Seow Y, Yin H, et al. Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat Biotechnol. 2011;29:306–309.
   Web of Science ®Google Scholar
• Tian Y, et al. A doxorubicin delivery platform using engineered natural membrane vesicle exosomes for targeted tumor therapy. Biomaterials. 2014;35:2383–2390.
   PubMed Web of Science ®Google Scholar
• Didiot MC, et al. Exosome-mediated delivery of hydrophobically modified siRNA for huntingtin mRNA silencing. Mol Ther. 2016;24:1836–1847.
   PubMed Web of Science ®Google Scholar
• Ohno S, et al. Systemically injected exosomes targeted to EGFR deliver antitumor MicroRNA to breast cancer cells. Mol Ther. 2012;21:185–191.
   Web of Science ®Google Scholar
• Zhuang X, et al. Treatment of brain inflammatory diseases by delivering exosome encapsulated anti-inflammatory drugs from the nasal region to the brain. Mol Ther. 2011;19:1769–1779.
   PubMed Web of Science ®Google Scholar
• Morelli AE, et al. Endocytosis, intracellular sorting, and processing of exosomes by dendritic cells. Blood. 2004;104:3257–3266.
   PubMed Web of Science ®Google Scholar
• Suetsugu A, et al. Imaging exosome transfer from breast cancer cells to stroma at metastatic sites in orthotopic nude-mouse models. Adv Drug Deliv Rev. 2013;65:383.
   PubMed Web of Science ®Google Scholar
• Tian T, Wang Y, Wang H, et al. Visualizing of the cellular uptake and intracellular trafficking of exosomes by live-cell microscopy. J Cell Biochem. 2010;111:488–496.
   PubMed Web of Science ®Google Scholar
• Feng D, et al. Cellular internalization of exosomes occurs through phagocytosis. Traffic. 2010;11:675–687.
   PubMed Web of Science ®Google Scholar
• Wiklander OPB, et al. Extracellular vesicle in vivo biodistribution is determined by cell source, route of administration and targeting. J Extracell Vesicles. 2015;4:26316.
   PubMed Web of Science ®Google Scholar
• Hood JL, San Roman S, Wickline SA. Exosomes released by melanoma cells prepare sentinel lymph nodes for tumor metastasis. Cancer Res. 2011;71:3792–3801.
   PubMed Web of Science ®Google Scholar
• Yang Y, et al. Exosomes mediate hepatitis B virus (HBV) transmission and NK-cell dysfunction. Cell Mol Immunol. 2017;14:465–475.
   PubMed Web of Science ®Google Scholar
• Pospichalova V, et al. Simplified protocol for flow cytometry analysis of fluorescently labeled exosomes and microvesicles using dedicated flow cytometer. J Extracell Vesicles. 2015;4:1–15.
   Web of Science ®Google Scholar
• Morales-kastresana A, et al. Labeling extracellular vesicles for nanoscale flow cytometry. Scientific Reports. 2017; 1–10. DOI:10.1038/s41598-017-01731-2
   Google Scholar
• Christianson HC, Svensson KJ, Kuppevelt TH, et al. Cancer cell exosomes depend on cell-surface heparan sulfate proteoglycans for their internalization and functional activity. Proc Natl Acad Sci USA. 2013 Oct 22;110(43):17380-17385. doi: 10.1073/pnas.1304266110. Epub 2013 Oct 7.
   Google Scholar
• Usman WM, et al. Efficient RNA drug delivery using red blood cell extracellular vesicles. Nat Commun. 2018 Jun 15;9(1):2359. doi: 10.1038/s41467-018-04791-8.
   Google Scholar
• Peinado H, et al. Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET. Nat Med. 2012 Jun;18(6):883–891. doi: 10.1038/nm.2753.
   Google Scholar
• Stoner SA, Duggan E, Condello D, et al. High sensitivity flow cytometry of membrane vesicles. Cytometry A. 2016 Feb;89(2):196206. –doi: 10.1002/cyto.a.22787. Epub 2015 Oct 20.
   Google Scholar
• Simonsen JB. Pitfalls associated with lipophilic fluorophore staining of extracellular vesicles for uptake studies. J Extracell Vesicles. 2019; 8(1): 1582237. Published online 2019 Feb 20. doi: 10.1080/20013078.2019.158223.
   Google Scholar
• De Rond L, Van Der Pol E, Hau CM, et al. Comparison of generic fluorescent markers for detection of extracellular vesicles by flow cytometry. Clin Chem. 2018 Apr;64(4):680–689. doi: 10.1373/clinchem.2017.278978. Epub 2018 Feb 16..
   Google Scholar
• Lai CP, et al. Visualization and tracking of tumour extracellular vesicle delivery and RNA translation using multiplexed reporters. Nat Commun. 2015;6.
   Web of Science ®Google Scholar
• Pužar Dominkuš P, et al. PKH26 labeling of extracellular vesicles: characterization and cellular internalization of contaminating PKH26 nanoparticles. Biochim Biophys Acta - Biomembr. 2018;1860:1350–1361.
   Web of Science ®Google Scholar
• Görgens A, et al. Optimisation of imaging flow cytometry for the analysis of single extracellular vesicles by using fluorescence-tagged vesicles as biological reference material. J Extracell Vesicles. 2019 Mar 21;8(1):1587567. doi: 10.1080/20013078.2019.1587567. eCollection 2019.
   Google Scholar
• Heusermann W, et al. Exosomes surf on filopodia to enter cells at endocytic hot spots, traffic within endosomes, and are targeted to the ER. J Cell Biol. 2016;213:173–184.
   PubMed Web of Science ®Google Scholar
• Kojima R, et al. Designer exosomes produced by implanted cells intracerebrally deliver therapeutic cargo for Parkinson’s disease treatment. Nat Commun. 2018;9.
   Web of Science ®Google Scholar
• Takahashi Y, et al. Visualization and in vivo tracking of the exosomes of murine melanoma B16-BL6 cells in mice after intravenous injection. J Biotechnol. 2013;165:77–84.
   PubMed Web of Science ®Google Scholar
• Zhang P, et al. In vivo tracking of multiple tumor exosomes labeled by phospholipid-based bioorthogonal conjugation. Anal Chem. 2018;90:11273–11279.
   Web of Science ®Google Scholar
• Delcayre A, et al. Exosome display technology: applications to the development of new diagnostics and therapeutics. Blood Cells Mol Dis. 2005;35:158.
   PubMed Web of Science ®Google Scholar
• Hartman ZC, et al. Increasing vaccine potency through exosome antigen targeting. Vaccine. 2011;29:9361–9367.
   PubMed Web of Science ®Google Scholar
• Rountree RB, et al. Exosome targeting of tumor antigens expressed by cancer vaccines can improve antigen immunogenicity and therapeutic efficacy. Cancer Res. 2011;71:5235–5244.
   PubMed Web of Science ®Google Scholar
• Zeelenberg IS, et al. Targeting tumor antigens to secreted membrane vesicles in vivo induces efficient antitumor immune responses. Cancer Res. 2008;68:1228–1235.
   PubMed Web of Science ®Google Scholar
• Gao X, et al. Anchor peptide captures, targets, and loads exosomes of diverse origins for diagnostics and therapy. Sci Transl Med. 2018;10:eaat0195.
   Web of Science ®Google Scholar
• Escola JM, et al. Selective enrichment of tetraspan proteins on the internal vesicles of multivesicular endosomes and on exosomes secreted by human B-lymphocytes. J Biol Chem. 1998;273:20121–20127.
   PubMed Web of Science ®Google Scholar
• Berditchevski F, Zutter MM, Hemler ME. Characterization of novel complexes on the cell surface between integrins and proteins with 4 transmembrane domains (TM4 proteins). Mol Biol Cell. 1996;7:193–207.
   PubMed Web of Science ®Google Scholar
• Latysheva N, et al. Syntenin-1 is a new component of tetraspanin-enriched microdomains: mechanisms and consequences of the interaction of syntenin-1 with CD63. Mol Cell Biol. 2006;26:7707–7718.
   PubMed Web of Science ®Google Scholar
• Radford KJ, Thorne RF, Hersey P. CD63 associates with transmembrane 4 superfamily members, CD9 and CD81, and with β1 integrins in human melanoma. Biochem Biophys Res Commun. 1996;222:13–18.
   PubMed Web of Science ®Google Scholar
• Théry C, Amigorena S, Raposo G, et al. Isolation and characterization of exosomes from cell culture supernatants and biological fluids. Curr Protoc Cell Biol. 2006 Apr; Chapter 3:Unit 3.22. doi: 10.1002/0471143030.cb0322s30.
   Google Scholar
• Willms E, et al. Cells release subpopulations of exosomes with distinct molecular and biological properties. Sci Rep. 2016;6:1–12.
   Web of Science ®Google Scholar
• Nordin JZ, et al. Ultrafiltration with size-exclusion liquid chromatography for high yield isolation of extracellular vesicles preserving intact biophysical and functional properties. Nanomedicine Nanotechnology, Biol Med. 2015;11:879–883.
   PubMed Web of Science ®Google Scholar
• Tabb DL, et al. Repeatability and reproducibility in proteomic identifications by liquid chromatography-tandem mass spectrometry. J Proteome Res. 2010. DOI:10.1021/pr9006365.
   Web of Science ®Google Scholar
• Ehrenberg M, Rigler R. Rotational brownian motion and fluorescence intensify fluctuations. Chem Phys. 1974. DOI:10.1016/0301-0104(74)85005-6
   Web of Science ®Google Scholar
• Magde D, Elson E, Webb WW. Thermodynamic fluctuations in a reacting system measurement by fluorescence correlation spectroscopy. Phys Rev Lett. 1972. DOI:10.1103/PhysRevLett.29.705
   Web of Science ®Google Scholar
• Kowal J, et al. Proteomic comparison defines novel markers to characterize heterogeneous populations of extracellular vesicle subtypes. Proc Natl Acad Sci. 2016;113:E968–E977.
   PubMed Web of Science ®Google Scholar
• Yoshioka Y, et al. Comparative marker analysis of extracellular vesicles in different human cancer types. J Extracell Vesicles. 2013;2:1–9.
   Google Scholar
• Baietti MF, et al. Syndecan–syntenin–ALIX regulates the biogenesis of exosomes. Nat Cell Biol. 2012;14:677–685.
   PubMed Web of Science ®Google Scholar
• Lötvall J, et al. Minimal experimental requirements for definition of extracellular vesicles and their functions: a position statement from the international society for extracellular vesicles. J Extracell Vesicles. 2014;3:26913.
   PubMedGoogle Scholar
• Trajkovic K, et al. Ceramide triggers budding of exosome vesicles into multivesicular endosomes. Science. 2008;319:1244–1247.
   PubMed Web of Science ®Google Scholar
• Otto GP, Nichols BJ. The roles of flotillin microdomains - endocytosis and beyond. J Cell Sci. 2011;124:3933–3940.
   PubMed Web of Science ®Google Scholar
• Myokai F, Takashiba S, Lebo R, et al. A novel lipopolysaccharide-induced transcription factor regulating tumor necrosis factor alpha gene expression: molecular cloning, sequencing, characterization, and chromosomal assignment. Proc Natl Acad Sci U S A. 1999;96:4518–4523.
   PubMed Web of Science ®Google Scholar
• Zhu H, et al. Mutation of SIMPLE in Charcot-Marie-Tooth 1C alters production of exosomes. Mol Biol Cell. 2013;24:1619–37, S1–3.
   Web of Science ®Google Scholar
• Shen B, Wu N, Yang J, et al. Protein targeting to exosomes/microvesicles by plasma membrane anchors *. J Biol Chem. 2011 Apr 22;286(16):14383–14395. doi: 10.1074/jbc.M110.208660. Epub 2011 Feb 7.
   Google Scholar
• Cheng Y, Schorey JS. Targeting soluble proteins to exosomes using a ubiquitin tag. Biotechnol Bioeng. 2015;113:1315–1324.
   Web of Science ®Google Scholar
• Katzmann DJ, Babst M, Emr SD. Ubiquitin-dependent sorting into the multivesicular body pathway requires the function of a conserved endosomal protein sorting complex, ESCRT-I. Cell. 2001;106:145–155.
   PubMed Web of Science ®Google Scholar
• Lässer C, et al. Two distinct extracellular RNA signatures released by a single cell type identified by microarray and next-generation sequencing. RNA Biol. 2017;14:58–72.
   PubMed Web of Science ®Google Scholar
• Willms E, Cabañas C, Mäger I, et al. Extracellular vesicle heterogeneity: subpopulations, isolation techniques, and diverse functions in cancer progression. Front Immunol. 2018;9.
   Web of Science ®Google Scholar
• Lee K, et al. Multiplexed profiling of single extracellular vesicles. ACS Nano. 2018. DOI:10.1021/acsnano.7b07060.
   Web of Science ®Google Scholar
• Aalberts M, et al. Quantitative and qualitative flow cytometric analysis of nanosized cell-derived membrane vesicles. Nanomedicine Nanotechnology, Biol Med. 2011;8:712–720.
   Web of Science ®Google Scholar
• Smith ZJ, et al. Single exosome study reveals subpopulations distributed among cell lines with variability related to membrane content. J Extracell Vesicles. 2015;4.
   Web of Science ®Google Scholar
• Stalder L, et al. The rough endoplasmatic reticulum is a central nucleation site of siRNA-mediated RNA silencing. Embo J. 2013;32:1115–1127.
   PubMed Web of Science ®Google Scholar
• Chevillet JR, et al. Quantitative and stoichiometric analysis of the microRNA content of exosomes. Proc Natl Acad Sci U S A. 2014;111:14888–14893.
   PubMed Web of Science ®Google Scholar
• Hung ME, Leonard JN. Stabilization of exosome-targeting peptides via engineered glycosylation. J Biol Chem. 2015;290:8166–8172.
   PubMed Web of Science ®Google Scholar
• Corso G, et al. Reproducible and scalable purification of extracellular vesicles using combined bind-elute and size exclusion chromatography. Sci Rep. 2017;7:11561.
   Web of Science ®Google Scholar
• El-Andaloussi S, et al. Exosome-mediated delivery of siRNA in vitro and in vivo. Nat Protoc. 2012;7:2112–2126.
   PubMed Web of Science ®Google Scholar
• Michaloglou C, et al. The tyrosine phosphatase PTPN14 is a negative regulator of YAP activity. PLoS One. 2013;8:e61916.
   PubMed Web of Science ®Google Scholar