Exosomes as therapeutics: The implications of molecular composition and exosomal heterogeneity

Journal of Controlled Release

Volumn 228, Issue , 2016, Pages 179-190

  Ferguson, Scott W ^a   Nguyen, Juliane ^a  

^a UNIVERSITY AT BUFFALO   (United States)

Author keywords

Exosomes; Heterogeneity; Lipids; Non coding RNAs; Proteins

Indexed keywords

AUTOMOBILE MANUFACTURE; LIPIDS; NUCLEIC ACIDS; PROTEINS; REVERSE ENGINEERING; RNA;

ANALYTICAL METHOD; CLINICAL TRANSLATION; EXOSOMES; HETEROGENEITY; MOLECULAR COMPOSITIONS; NON-CODING RNAS; THERAPEUTIC DRUG DELIVERY; THERAPEUTIC EFFECTS;

DRUG DELIVERY;

CELL PROTEIN; DRUG CARRIER; EPITHELIAL CELL ADHESION MOLECULE; LIPID; MESSENGER RNA; MICRORNA; NUCLEIC ACID; UNTRANSLATED RNA; PROTEIN; RNA;

BIOGENESIS; BIOLOGICAL ACTIVITY; CANCER CELL; CANCER STEM CELL; CELL ACTIVATION; CELL COMPOSITION; CELL HETEROGENEITY; CELL MEMBRANE; CELL SUBPOPULATION; DRUG DELIVERY SYSTEM; ELECTROPORATION; EXOSOME; FLOW CYTOMETRY; HUMAN; LIPID COMPOSITION; MULTIVESICULAR BODY; NONHUMAN; NUCLEOTIDE SEQUENCE; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN POLYMORPHISM; REVERSE ENGINEERING; REVIEW; RNA ANALYSIS; RNA SEQUENCE; SIGNAL TRANSDUCTION; ANIMAL; CHEMISTRY; GENE TRANSFER; LIPID METABOLISM; METABOLISM; PROCEDURES;

ANIMALS; DRUG CARRIERS; DRUG DELIVERY SYSTEMS; EXOSOMES; GENE TRANSFER TECHNIQUES; HUMANS; LIPID METABOLISM; LIPIDS; PROTEINS; RNA;

EID: 84960842751     PISSN: 01683659     EISSN: 18734995     Source Type: Journal    
DOI: 10.1016/j.jconrel.2016.02.037     Document Type: Review

References (124)

1. E.G. Trams, C.J. Lauter, N. Salem Jr., and U. Heine Exfoliation of membrane ecto-enzymes in the form of micro-vesicles Biochim. Biophys. Acta 645 1 1981 63 70
2. L. Alvarez-Erviti, Y. Seow, H. Yin, C. Betts, S. Lakhal, and M.J. Wood Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes Nat. Biotechnol. 29 4 2011 341 345
3. K. Bryniarski, W. Ptak, A. Jayakumar, K. Pullmann, M.J. Caplan, A. Chairoungdua, J. Lu, B.D. Adams, E. Sikora, K. Nazimek, S. Marquez, S.H. Kleinstein, P. Sangwung, Y. Iwakiri, E. Delgato, F. Redegeld, B.R. Blokhuis, J. Wojcikowski, A.W. Daniel, T. Groot Kormelink, and P.W. Askenase Antigen-specific, antibody-coated, exosome-like nanovesicles deliver suppressor T-cell microRNA-150 to effector T cells to inhibit contact sensitivity J. Allergy Clin. Immunol. 132 1 2013 170 181
4. L. Chen, A. Charrier, Y. Zhou, R. Chen, B. Yu, K. Agarwal, H. Tsukamoto, L.J. Lee, M.E. Paulaitis, and D.R. Brigstock Epigenetic regulation of connective tissue growth factor by MicroRNA-214 delivery in exosomes from mouse or human hepatic stellate cells Hepatology 59 3 2014 1118 1129
5. J.M. Cooper, P.B. Wiklander, J.Z. Nordin, R. Al-Shawi, M.J. Wood, M. Vithlani, A.H. Schapira, J.P. Simons, S. El-Andaloussi, and L. Alvarez-Erviti Systemic exosomal siRNA delivery reduced alpha-synuclein aggregates in brains of transgenic mice Mov. Disord. 29 12 2014 1476 1485
6. J.P. de Rivero Vaccari, F. Brand 3rd, S. Adamczak, S.W. Lee, J. Perez-Barcena, M.Y. Wang, M.R. Bullock, W.D. Dietrich, and R.W. Keane Exosome-mediated inflammasome signaling after central nervous system injury J. Neurochem. 136 Suppl. 1 2016 39 48
7. Y. Feng, W. Huang, M. Wani, X. Yu, and M. Ashraf Ischemic preconditioning potentiates the protective effect of stem cells through secretion of exosomes by targeting Mecp2 via miR-22 PLoS ONE 9 2 2014 e8e8685
8. M. Grapp, A. Wrede, M. Schweizer, S. Hüwel, H.-J. Galla, N. Snaidero, M. Simons, J. Bückers, P.S. Low, H. Urlaub, J. Gärtner, and R. Steinfeld Choroid plexus transcytosis and exosome shuttling deliver folate into brain parenchyma Nat. Commun. 4 2013
9. J. Halkein, S.P. Tabruyn, M. Ricke-Hoch, A. Haghikia, N.-Q.-N. Nguyen, M. Scherr, K. Castermans, L. Malvaux, V. Lambert, M. Thiry, K. Sliwa, A. Noel, J.A. Martial, D. Hilfiker-Kleiner, and I. Struman MicroRNA-146a is a therapeutic target and biomarker for peripartum cardiomyopathy J. Clin. Invest. 123 5 2013 2143 2154
10. S. Ju, J. Mu, T. Dokland, X. Zhuang, Q. Wang, H. Jiang, X. Xiang, Z.B. Deng, B. Wang, L. Zhang, M. Roth, R. Welti, J. Mobley, Y. Jun, D. Miller, and H.G. Zhang Grape exosome-like nanoparticles induce intestinal stem cells and protect mice from DSS-induced colitis Mol. Ther. 21 7 2013 1345 1357
11. M. Katakowski, B. Buller, X. Zheng, Y. Lu, T. Rogers, O. Osobamiro, W. Shu, F. Jiang, and M. Chopp Exosomes from marrow stromal cells expressing miR-146b inhibit glioma growth Cancer Lett. 335 1 2013 201 204
12. D.K. Kim, H. Nishida, S.Y. An, A.K. Shetty, T.J. Bartosh, and D.J. Prockop Chromatographically isolated CD63 + CD81 + extracellular vesicles from mesenchymal stromal cells rescue cognitive impairments after TBI Proc. Natl. Acad. Sci. U. S. A. 113 1 2016 170 175
13. N. Kosaka, H. Iguchi, Y. Yoshioka, K. Hagiwara, F. Takeshita, and T. Ochiya Competitive interactions of cancer cells and normal cells via secretory microRNAs J. Biol. Chem. 287 2 2012 1397 1405
14. Y.S. Lee, S.H. Kim, J.A. Cho, and C.W. Kim Introduction of the CIITA gene into tumor cells produces exosomes with enhanced anti-tumor effects Exp. Mol. Med. 43 2011 281 290
15. Y. Liu, D. Li, Z. Liu, Y. Zhou, D. Chu, X. Li, X. Jiang, D. Hou, X. Chen, Y. Chen, Z. Yang, L. Jin, W. Jiang, C. Tian, G. Zhou, K. Zen, J. Zhang, Y. Zhang, J. Li, and C.Y. Zhang Targeted exosome-mediated delivery of opioid receptor Mu siRNA for the treatment of morphine relapse Sci. Rep. 5 2015 17543
16. A. Mizrak, M.F. Bolukbasi, G.B. Ozdener, G.J. Brenner, S. Madlener, E.P. Erkan, T. Strobel, X.O. Breakefield, and O. Saydam Genetically engineered microvesicles carrying suicide mRNA/protein inhibit schwannoma tumor growth Mol. Ther. 21 1 2013 101 108
17. J.L. Munoz, S.A. Bliss, S.J. Greco, S.H. Ramkissoon, K.L. Ligon, and P. Rameshwar Delivery of functional anti-miR-9 by mesenchymal stem cell-derived exosomes to glioblastoma multiforme cells conferred chemosensitivity Mol. Ther. Nucleic Acids 2 2013 e126
18. K. O'Brien, M.C. Lowry, C. Corcoran, V.G. Martinez, M. Daly, S. Rani, W.M. Gallagher, M.W. Radomski, R.A. MacLeod, and L. O'Driscoll miR-134 in extracellular vesicles reduces triple-negative breast cancer aggression and increases drug sensitivity Oncotarget 6 32 2015 32774 32789
19. S. Ohno, M. Takanashi, K. Sudo, S. Ueda, A. Ishikawa, N. Matsuyama, K. Fujita, T. Mizutani, T. Ohgi, T. Ochiya, N. Gotoh, and M. Kuroda Systemically injected exosomes targeted to EGFR deliver antitumor microRNA to breast cancer cells Mol. Ther. 21 1 2013 185 191
20. Q. Pan, V. Ramakrishnaiah, S. Henry, S. Fouraschen, P.E. de Ruiter, J. Kwekkeboom, H.W. Tilanus, H.L.A. Janssen, and L.J.W. van der Laan Hepatic cell-to-cell transmission of small silencing RNA can extend the therapeutic reach of RNA interference (RNAi) Gut 61 9 2012 1330 1339
21. T.A. Shtam, R.A. Kovalev, E.Y. Varfolomeeva, E.M. Makarov, Y.V. Kil, and M.V. Filatov Exosomes are natural carriers of exogenous siRNA to human cells in vitro Cell Commun. Signal. 11 2013 88
22. J. Wahlgren, L.K.T. De, M. Brisslert, F. Vaziri Sani, E. Telemo, P. Sunnerhagen, and H. Valadi Plasma exosomes can deliver exogenous short interfering RNA to monocytes and lymphocytes Nucleic Acids Res. 40 17 2012 e130
23. H. Xin, Y. Li, B. Buller, M. Katakowski, Y. Zhang, X. Wang, X. Shang, Z.G. Zhang, and M. Chopp Exosome-mediated transfer of miR-133b from multipotent mesenchymal stromal cells to neural cells contributes to neurite outgrowth Stem Cells 30 7 2012 1556 1564
24. H. Xin, Y. Li, Y. Cui, J.J. Yang, Z.G. Zhang, and M. Chopp Systemic administration of exosomes released from mesenchymal stromal cells promote functional recovery and neurovascular plasticity after stroke in rats J. Cereb. Blood Flow Metab. 33 11 2013 1711 1715
25. Y. Zhang, M. Chopp, Y. Meng, M. Katakowski, H. Xin, A. Mahmood, and Y. Xiong Effect of exosomes derived from multipluripotent mesenchymal stromal cells on functional recovery and neurovascular plasticity in rats after traumatic brain injury J. Neurosurg. 122 4 2015 856 867
26. Y. Zhao, M.J. Haney, R. Gupta, J.P. Bohnsack, Z. He, A.V. Kabanov, and E.V. Batrakova GDNF-transfected macrophages produce potent neuroprotective effects in Parkinson's disease mouse model PLoS ONE 9 9 2014 e106867
27. Y. Zhou, L. Fang, Y. Yu, J. Niu, L. Jiang, H. Cao, Q. Sun, K. Zen, C. Dai, and J. Yang Erythropoietin protects the tubular basement membrane by promoting the bone marrow to release extracellular vesicles containing tPA-targeting miR-144 Am. J. Physiol. Ren. Physiol. 310 1 2016 F27 F40
28. J.M. Aliotta, M. Pereira, K.W. Johnson, N. de Paz, M.S. Dooner, N. Puente, C. Ayala, K. Brilliant, D. Berz, D. Lee, B. Ramratnam, P.N. McMillan, D.C. Hixson, D. Josic, and P.J. Quesenberry Microvesicle entry into marrow cells mediates tissue-specific changes in mRNA by direct delivery of mRNA and induction of transcription Exp. Hematol. 38 3 2010 233 245
29. G. Camussi, M.C. Deregibus, S. Bruno, V. Cantaluppi, and L. Biancone Exosomes/microvesicles as a mechanism of cell-to-cell communication Kidney Int. 78 9 2010 838 848
30. S.S. Luo, O. Ishibashi, G. Ishikawa, T. Ishikawa, A. Katayama, T. Mishima, T. Takizawa, T. Shigihara, T. Goto, A. Izumi, A. Ohkuchi, S. Matsubara, T. Takeshita, and T. Takizawa Human villous trophoblasts express and secrete placenta-specific MicroRNAs into maternal circulation via exosomes Biol. Reprod. 81 4 2009 717 729
31. C. Thery Exosomes: secreted vesicles and intercellular communications. F1000 Biol. Reprod. 3 2011 15
32. C. Kahlert, and R. Kalluri Exosomes in tumor microenvironment influence cancer progression and metastasis J. Mol. Med. 91 4 2013 431 437
33. M. Mittelbrunn, C. Gutierrez-Vazquez, C. Villarroya-Beltri, S. Gonzalez, F. Sanchez-Cabo, M.A. Gonzalez, A. Bernad, and F. Sanchez-Madrid Unidirectional transfer of microRNA-loaded exosomes from T cells to antigen-presenting cells Nat. Commun. 2 2011 282
34. I.S. Okoye, S.M. Coomes, V.S. Pelly, S. Czieso, V. Papayannopoulos, T. Tolmachova, M.C. Seabra, and M.S. Wilson MicroRNA-containing T-regulatory-cell-derived exosomes suppress pathogenic T helper 1 cells Immunity 41 1 2014 89 103
35. J. Wahlgren, L. Karlson Tde, P. Glader, E. Telemo, and H. Valadi Activated human T cells secrete exosomes that participate in IL-2 mediated immune response signaling PLoS ONE 7 11 2012 e49723
36. F. Arslan, R.C. Lai, M.B. Smeets, L. Akeroyd, A. Choo, E.N. Aguor, L. Timmers, H.V. van Rijen, P.A. Doevendans, G. Pasterkamp, S.K. Lim, and D.P. de Kleijn 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 3 2013 301 312
37. E.V. Batrakova, and M.S. Kim Using exosomes, naturally-equipped nanocarriers, for drug delivery J. Control. Release 219 2015 396 405
38. J. Lotvall, A.F. Hill, F. Hochberg, E.I. Buzas, D. Di Vizio, C. Gardiner, Y.S. Gho, I.V. Kurochkin, S. Mathivanan, P. Quesenberry, S. Sahoo, H. Tahara, M.H. Wauben, K.W. Witwer, and C. Thery Minimal experimental requirements for definition of extracellular vesicles and their functions: A position statement from the International Society for Extracellular Vesicles J. Extracellular Vesicles 3 2014 26913
39. ClinicalTrials.gov https://wwwclinicaltrialsgov/ct2/results?term=exosome&Search=Search 2015
40. M. Record Exosomal Lipids in Cell-Cell Communication H.-G. Zhang, Emerging Concepts of Tumor Exosome-Mediated Cell-Cell Communication 2013 Springer New York 47 68
41. S.J. Gould, and G. Raposo As we wait: coping with an imperfect nomenclature for extracellular vesicles 2013 2013
42. J. Kowal, M. Tkach, and C. Thery Biogenesis and secretion of exosomes Curr. Opin. Cell Biol. 29 2014 116 125
43. C. Thery, S. Amigorena, G. Raposo, and A. Clayton Isolation and characterization of exosomes from cell culture supernatants and biological fluids Curr. Protoc. Cell Biol. Chapter 3 Unit 3 22 2006
44. B. György, T.G. Szabó, M. Pásztói, Z. Pál, P. Misják, B. Aradi, V. László, É. Pállinger, E. Pap, Á. Kittel, G. Nagy, A. Falus, and E.I. Buzás Membrane vesicles, current state-of-the-art: emerging role of extracellular vesicles Cell. Mol. Life Sci. 68 16 2011 2667 2688
45. R. Wubbolts, R.S. Leckie, P.T. Veenhuizen, G. Schwarzmann, W. Mobius, J. Hoernschemeyer, J.W. Slot, H.J. Geuze, and W. Stoorvogel Proteomic and biochemical analyses of human B cell-derived exosomes. potential implications for their function and multivesicular body formation J. Biol. Chem. 278 13 2003 10963 10972
46. S.-M. Chung, O.-N. Bae, K.-M. Lim, J.-Y. Noh, M.-Y. Lee, Y.-S. Jung, and J.-H. Chung Lysophosphatidic acid induces thrombogenic activity through phosphatidylserine exposure and procoagulant microvesicle generation in human erythrocytes Arterioscler. Thromb. Vasc. Biol. 27 2 2007 414 421
47. H.F. Heijnen, A.E. Schiel, R. Fijnheer, H.J. Geuze, and J.J. Sixma Activated platelets release two types of membrane vesicles: microvesicles by surface shedding and exosomes derived from exocytosis of multivesicular bodies and alpha-granules Blood 94 11 1999 3791 3799
48. B.W.M. van Balkom, A.S. Eisele, D.M. Pegtel, S. Bervoets, and M.C. Verhaar Quantitative and Qualitative Analysis of Small RNAs in Human Endothelial Cells and Exosomes Provides Insights Into Localized RNA Processing, Degradation and Sorting 2015
49. N. Yamada, N. Tsujimura, M. Kumazaki, H. Shinohara, K. Taniguchi, Y. Nakagawa, T. Naoe, and Y. Akao Colorectal cancer cell-derived microvesicles containing microRNA-1246 promote angiogenesis by activating Smad 1/5/8 signaling elicited by PML down-regulation in endothelial cells Biochim. Biophys. Acta (BBA) Gene Regul. Mech. 1839 11 2014 1256 1272
50. J. Van Deun, P. Mestdagh, R. Sormunen, V. Cocquyt, K. Vermaelen, J. Vandesompele, M. Bracke, O. De Wever, and A. Hendrix The impact of disparate isolation methods for extracellular vesicles on downstream RNA profiling J. Extracellular Vesicles 3 2014
51. K. Laulagnier, H. Vincent-Schneider, S. Hamdi, C. Subra, D. Lankar, and M. Record Characterization of exosome subpopulations from RBL-2H3 cells using fluorescent lipids Blood Cells Mol. Dis. 35 2 2005 116 121
52. Z.J. Smith, C. Lee, T. Rojalin, R.P. Carney, S. Hazari, A. Knudson, K. Lam, H. Saari, E.L. Ibanez, T. Viitala, T. Laaksonen, M. Yliperttula, and S. Wachsmann-Hogiu Single exosome study reveals subpopulations distributed among cell lines with variability related to membrane content J. Extracellular Vesicles 4 2015 28533
53. M.P. Oksvold, A. Kullmann, L. Forfang, B. Kierulf, M. Li, A. Brech, A.V. Vlassov, E.B. Smeland, A. Neurauter, and K.W. Pedersen Expression of B-cell surface antigens in subpopulations of exosomes released from B-cell lymphoma cells Clin. Ther. 36 6 2014 847 862 (e841)
54. B. Roucourt, S. Meeussen, J. Bao, P. Zimmermann, and G. David Heparanase activates the syndecan-syntenin-ALIX exosome pathway Cell Res. 25 4 2015 412 428
55. B.J. Tauro, D.W. Greening, R.A. Mathias, S. Mathivanan, H. Ji, and R.J. Simpson Two distinct populations of exosomes are released from LIM1863 colon carcinoma cell-derived organoids Mol. Cell. Proteomics 12 3 2013 587 598
56. E. van der Pol, F. Coumans, Z. Varga, M. Krumrey, and R. Nieuwland Innovation in detection of microparticles and exosomes J. Thromb. Haemost. 11 2013 36 45
57. V. Pospichalova, J. Svoboda, Z. Dave, A. Kotrbova, K. Kaiser, D. Klemova, L. Ilkovics, A. Hampl, I. Crha, E. Jandakova, L. Minar, V. Weinberger, and V. Bryja Simplified protocol for flow cytometry analysis of fluorescently labeled exosomes and microvesicles using dedicated flow cytometer J. Extracellular Vesicles 4 2015 25530
58. E.J. van der Vlist, E.N. Nolte-'t Hoen, W. Stoorvogel, G.J. Arkesteijn, and M.H. Wauben Fluorescent labeling of nano-sized vesicles released by cells and subsequent quantitative and qualitative analysis by high-resolution flow cytometry Nat. Protoc. 7 7 2012 1311 1326
59. J.R. Chevillet, Q. Kang, I.K. Ruf, H.A. Briggs, L.N. Vojtech, S.M. Hughes, H.H. Cheng, J.D. Arroyo, E.K. Meredith, E.N. Gallichotte, E.L. Pogosova-Agadjanyan, C. Morrissey, D.L. Stirewalt, F. Hladik, E.Y. Yu, C.S. Higano, and M. Tewari Quantitative and stoichiometric analysis of the microRNA content of exosomes Proc. Natl. Acad. Sci. U. S. A. 111 41 2014 14888 14893
60. S.A. Kooijmans, S. Stremersch, K. Braeckmans, S.C. de Smedt, A. Hendrix, M.J. Wood, R.M. Schiffelers, K. Raemdonck, and P. Vader Electroporation-induced siRNA precipitation obscures the efficiency of siRNA loading into extracellular vesicles J. Control. Release 172 1 2013 229 238
61. T.N. Lamichhane, R.S. Raiker, and S.M. Jay Exogenous DNA Loading into extracellular vesicles via electroporation is size-dependent and enables limited gene delivery Mol. Pharm. 12 10 2015 3650 3657
62. O. Rechavi, Y. Erlich, H. Amram, L. Flomenblit, F.V. Karginov, I. Goldstein, G.J. Hannon, and Y. Kloog Cell contact-dependent acquisition of cellular and viral nonautonomously encoded small RNAs Genes Dev. 23 16 2009 1971 1979
63. C. Villarroya-Beltri, C. Gutierrez-Vazquez, F. Sanchez-Cabo, D. Perez-Hernandez, J. Vazquez, N. Martin-Cofreces, D.J. Martinez-Herrera, A. Pascual-Montano, M. Mittelbrunn, and F. Sanchez-Madrid Sumoylated hnRNPA2B1 controls the sorting of miRNAs into exosomes through binding to specific motifs Nat. Commun. 4 2013 2980
64. D. Koppers-Lalic, M. Hackenberg, I.V. Bijnsdorp, M.A. van Eijndhoven, P. Sadek, D. Sie, N. Zini, J.M. Middeldorp, B. Ylstra, R.X. de Menezes, T. Wurdinger, G.A. Meijer, and D.M. Pegtel Nontemplated nucleotide additions distinguish the small RNA composition in cells from exosomes Cell Rep. 8 6 2014 1649 1658
65. M.F. Bolukbasi, A. Mizrak, G.B. Ozdener, S. Madlener, T. Strobel, E.P. Erkan, J.B. Fan, X.O. Breakefield, and O. Saydam miR-1289 and "Zipcode"-like sequence enrich mRNAs in microvesicles Mol. Ther. Nucleic Acids 1 2012 e10
66. A.O. Batagov, V.A. Kuznetsov, and I.V. Kurochkin Identification of nucleotide patterns enriched in secreted RNAs as putative cis-acting elements targeting them to exosome nano-vesicles BMC Genomics 12 2011
67. A.E. Hall, C. Turnbull, and T. Dalmay Y RNAs: recent developments Biomol. Concepts 4 2 2013 103 110
68. C.P. Christov, T.J. Gardiner, D. Szuts, and T. Krude Functional requirement of noncoding Y RNAs for human chromosomal DNA replication Mol. Cell. Biol. 26 18 2006 6993 7004
69. S. Hussain, A.A. Sajini, S. Blanco, S. Dietmann, P. Lombard, Y. Sugimoto, M. Paramor, J.G. Gleeson, D.T. Odom, J. Ule, and M. Frye NSun2-mediated cytosine-5 methylation of vault noncoding RNA determines its processing into regulatory small RNAs Cell Rep. 4 2 2013 255 261
70. H. Persson, A. Kvist, J. Vallon-Christersson, P. Medstrand, A. Borg, and C. Rovira The non-coding RNA of the multidrug resistance-linked vault particle encodes multiple regulatory small RNAs Nat. Cell Biol. 11 10 2009 1268 1271
71. S.C. Gopinath, R. Wadhwa, and P.K. Kumar Expression of noncoding vault RNA in human malignant cells and its importance in mitoxantrone resistance Mol. Cancer Res. 8 11 2010 1536 1546
72. S.R. Baglio, K. Rooijers, D. Koppers-Lalic, F.J. Verweij, M. Perez Lanzon, N. Zini, B. Naaijkens, F. Perut, H.W. Niessen, N. Baldini, and D.M. Pegtel Human bone marrow- and adipose-mesenchymal stem cells secrete exosomes enriched in distinctive miRNA and tRNA species Stem Cell Res. Ther. 6 2015 127
73. P. Jenjaroenpun, Y. Kremenska, V.M. Nair, M. Kremenskoy, B. Joseph, and I.V. Kurochkin Characterization of RNA in exosomes secreted by human breast cancer cell lines using next-generation sequencing Peer J. 1 2013 e201
74. M. Li, E. Zeringer, T. Barta, J. Schageman, A. Cheng, and A.V. Vlassov Analysis of the RNA content of the exosomes derived from blood serum and urine and its potential as biomarkers Philos. Trans. R. Soc. Lond. Ser. B Biol. Sci. 369 1652 2014
75. J. Schageman, E. Zeringer, M. Li, T. Barta, K. Lea, J. Gu, S. Magdaleno, R. Setterquist, and A.V. Vlassov The complete exosome workflow solution: from isolation to characterization of RNA cargo Biomed. Res. Int. 2013 2013 253957
76. J.P. Tosar, F. Gambaro, J. Sanguinetti, B. Bonilla, K.W. Witwer, and A. Cayota Assessment of small RNA sorting into different extracellular fractions revealed by high-throughput sequencing of breast cell lines Nucleic Acids Res. 43 11 2015 5601 5616
77. C.C. Li, S.A. Eaton, P.E. Young, M. Lee, R. Shuttleworth, D.T. Humphreys, G.E. Grau, V. Combes, M. Bebawy, J. Gong, S. Brammah, M.E. Buckland, and C.M. Suter Glioma microvesicles carry selectively packaged coding and non-coding RNAs which alter gene expression in recipient cells RNA Biol. 10 8 2013 1333 1344
78. M. Ono, K. Yamada, F. Avolio, M.S. Scott, S. van Koningsbruggen, G.J. Barton, and A.I. Lamond Analysis of human small nucleolar RNAs (snoRNA) and the development of snoRNA modulator of gene expression vectors Mol. Biol. Cell 21 9 2010 1569 1584
79. X. Darzacq, B.E. Jady, C. Verheggen, A.M. Kiss, E. Bertrand, and T. Kiss Cajal body-specific small nuclear RNAs: A novel class of 2′-O-methylation and pseudouridylation guide RNAs EMBO J. 21 11 2002 2746 2756
80. P. Kumar, J. Anaya, S.B. Mudunuri, and A. Dutta Meta-analysis of tRNA derived RNA fragments reveals that they are evolutionarily conserved and associate with AGO proteins to recognize specific RNA targets BMC Biol. 12 2014 78
81. Q. Wang, I. Lee, J. Ren, S.S. Ajay, Y.S. Lee, and X. Bao Identification and functional characterization of tRNA-derived RNA fragments (tRFs) in respiratory syncytial virus infection Mol. Ther. 21 2 2013 368 379
82. S.A.A. Kooijmans, P. Vader, S.M. van Dommelen, W.W. van Solinge, and R.M. Schiffelers Exosome mimetics: A novel class of drug delivery systems Int. J. Nanomedicine 7 2012 1525 1541
83. A.E. Morelli, A.T. Larregina, W.J. Shufesky, M.L.G. Sullivan, D.B. Stolz, G.D. Papworth, A.F. Zahorchak, A.J. Logar, Z. Wang, S.C. Watkins, L.D. Falo, and A.W. Thomson Endocytosis, intracellular sorting, and processing of exosomes by dendritic cells Blood 104 10 2004 3257 3266
84. L.A. Mulcahy, R.C. Pink, and D.R.F. Carter Routes and mechanisms of extracellular vesicle uptake J. Extracellular Vesicles 3 2014 10.3402/jev.v3403.24641
85. Z. Andreu, and M. Yanez-Mo Tetraspanins in extracellular vesicle formation and function Front. Immunol. 5 2014 442
86. F. Gattazzo, A. Urciuolo, and P. Bonaldo Extracellular matrix: A dynamic microenvironment for stem cell niche Biochim. Biophys. Acta 1840 8 2014 2506 2519
87. P. Lu, K. Takai, V.M. Weaver, and Z. Werb Extracellular matrix degradation and remodeling in development and disease Cold Spring Harb. Perspect. Biol. 3 12 2011
88. D.A. Harris, S.H. Patel, M. Gucek, A. Hendrix, W. Westbroek, and J.W. Taraska Exosomes released from breast cancer carcinomas stimulate cell movement PLoS ONE 10 3 2015 e0117495
89. M.E. Hemler Tetraspanin proteins promote multiple cancer stages Nat. Rev. Cancer 14 1 2014 49 60
90. T. Iwasaki, Y. Takeda, K. Maruyama, Y. Yokosaki, K. Tsujino, S. Tetsumoto, H. Kuhara, K. Nakanishi, Y. Otani, Y. Jin, S. Kohmo, H. Hirata, R. Takahashi, M. Suzuki, K. Inoue, I. Nagatomo, S. Goya, T. Kijima, T. Kumagai, I. Tachibana, I. Kawase, and A. Kumanogoh Deletion of tetraspanin CD9 diminishes lymphangiogenesis in vivo and in vitro J. Biol. Chem. 288 4 2013 2118 2131
91. P. Shetty, A. Bargale, B.R. Patil, R. Mohan, U.S. Dinesh, J.K. Vishwanatha, P.B. Gai, V.S. Patil, and T.S. Amsavardani Cell surface interaction of annexin A2 and galectin-3 modulates epidermal growth factor receptor signaling in Her-2 negative breast cancer cells Mol. Cell. Biochem. 2015
92. M.M. Webber, and A. Waghray Urokinase-mediated extracellular matrix degradation by human prostatic carcinoma cells and its inhibition by retinoic acid Clin. Cancer Res. 1 7 1995 755 761
93. D.H. Hsu, P. Paz, G. Villaflor, A. Rivas, A. Mehta-Damani, E. Angevin, L. Zitvogel, and J.B. Le Pecq Exosomes as a tumor vaccine: enhancing potency through direct loading of antigenic peptides J. Immunother. 26 5 2003 440 450
94. H.G. Lamparski, A. Metha-Damani, J.Y. Yao, S. Patel, D.H. Hsu, C. Ruegg, and J.B. Le Pecq Production and characterization of clinical grade exosomes derived from dendritic cells J. Immunol. Methods 270 2 2002 211 226
95. M.A. Morse, J. Garst, T. Osada, S. Khan, A. Hobeika, T.M. Clay, N. Valente, R. Shreeniwas, M.A. Sutton, A. Delcayre, D.H. Hsu, J.B. Le Pecq, and H.K. Lyerly A phase I study of dexosome immunotherapy in patients with advanced non-small cell lung cancer J. Transl. Med. 3 1 2005 9
96. R.C. Lai, F. Arslan, M.M. Lee, N.S. Sze, A. Choo, T.S. Chen, M. Salto-Tellez, L. Timmers, C.N. Lee, R.M. El Oakley, G. Pasterkamp, D.P. de Kleijn, and S.K. Lim Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury Stem Cell Res. 4 3 2010 214 222
97. F.R. Formiga, B. Pelacho, E. Garbayo, I. Imbuluzqueta, P. Diaz-Herraez, G. Abizanda, J.J. Gavira, T. Simon-Yarza, E. Albiasu, E. Tamayo, F. Prosper, and M.J. Blanco-Prieto Controlled delivery of fibroblast growth factor-1 and neuregulin-1 from biodegradable microparticles promotes cardiac repair in a rat myocardial infarction model through activation of endogenous regeneration J. Control. Release 173 2014 132 139
98. X. Gu, X. Liu, D. Xu, X. Li, M. Yan, Y. Qi, W. Yan, W. Wang, J. Pan, Y. Xu, B. Xi, L. Cheng, J. Jia, K. Wang, J. Ge, and M. Zhou Cardiac functional improvement in rats with myocardial infarction by up-regulating cardiac myosin light chain kinase with neuregulin Cardiovasc. Res. 88 2 2010 334 343
99. M.F. Hill, A.V. Patel, A. Murphy, H.M. Smith, C.L. Galindo, L. Pentassuglia, X. Peng, C.G. Lenneman, O. Odiete, D.B. Friedman, M.W. Kronenberg, S. Zheng, Z. Zhao, Y. Song, F.E. Harrell Jr., M. Srinivas, A. Ganguly, J. Iaci, T.J. Parry, A.O. Caggiano, and D.B. Sawyer Intravenous glial growth factor 2 (GGF2) isoform of neuregulin-1beta improves left ventricular function, gene and protein expression in rats after myocardial infarction PLoS ONE 8 2 2013 e55741
100. J. Xiao, B. Li, Z. Zheng, M. Wang, J. Peng, Y. Li, and Z. Li Therapeutic effects of neuregulin-1 gene transduction in rats with myocardial infarction Coron. Artery Dis. 23 7 2012 460 468
101. M. Palmen, M.J. Daemen, L.J. De Windt, J. Willems, W.R. Dassen, S. Heeneman, R. Zimmermann, M. Van Bilsen, and P.A. Doevendans Fibroblast growth factor-1 improves cardiac functional recovery and enhances cell survival after ischemia and reperfusion: A fibroblast growth factor receptor, protein kinase C, and tyrosine kinase-dependent mechanism J. Am. Coll. Cardiol. 44 5 2004 1113 1123
102. T. Okazaki, S. Ebihara, M. Asada, S. Yamanda, Y. Saijo, Y. Shiraishi, T. Ebihara, K. Niu, H. Mei, H. Arai, and T. Yambe Macrophage colony-stimulating factor improves cardiac function after ischemic injury by inducing vascular endothelial growth factor production and survival of cardiomyocytes Am. J. Pathol. 171 4 2007 1093 1103
103. C. Zgheib, F.A. Zouein, M. Kurdi, and G.W. Booz Chronic treatment of mice with leukemia inhibitory factor does not cause adverse cardiac remodeling but improves heart function Eur. Cytokine Netw. 23 4 2012 191 197
104. C. Salomon, J. Ryan, L. Sobrevia, M. Kobayashi, K. Ashman, M. Mitchell, and G.E. Rice Exosomal signaling during hypoxia mediates microvascular endothelial cell migration and vasculogenesis PLoS ONE 8 7 2013 e68451
105. H. Mi, A. Muruganujan, and P.D. Thomas PANTHER in 2013: modeling the evolution of gene function, and other gene attributes, in the context of phylogenetic trees Nucleic Acids Res. 41 Database issue 2013 D377 D386
106. H. Mi, A. Muruganujan, J.T. Casagrande, and P.D. Thomas Large-scale gene function analysis with the PANTHER classification system Nat. Protoc. 8 8 2013 1551 1566
107. K. Carayon, K. Chaoui, E. Ronzier, I. Lazar, J. Bertrand-Michel, V. Roques, S. Balor, F. Terce, A. Lopez, L. Salomé, and E. Joly Proteolipidic composition of exosomes changes during reticulocyte maturation J. Biol. Chem. 286 39 2011 34426 34439
108. A. Llorente, T. Skotland, T. Sylvänne, D. Kauhanen, T. Róg, A. Orłowski, I. Vattulainen, K. Ekroos, and K. Sandvig Molecular lipidomics of exosomes released by PC-3 prostate cancer cells Biochim. Biophys. Acta (BBA) Mol. Cell Biol. Lipids 1831 7 2013 1302 1309
109. E.M. Kramer-Albers, N. Bretz, S. Tenzer, C. Winterstein, W. Mobius, H. Berger, K.A. Nave, H. Schild, and J. Trotter Oligodendrocytes secrete exosomes containing major myelin and stress-protective proteins: trophic support for axons? Proteomics Clin. Appl. 1 11 2007 1446 1461
110. C. von Haefen, T. Wieder, B. Gillissen, L. Starck, V. Graupner, B. Dorken, and P.T. Daniel Ceramide induces mitochondrial activation and apoptosis via a Bax-dependent pathway in human carcinoma cells Oncogene 21 25 2002 4009 4019
111. G. Wang, M. Dinkins, Q. He, G. Zhu, C. Poirier, A. Campbell, M. Mayer-Proschel, and E. Bieberich Astrocytes secrete exosomes enriched with proapoptotic ceramide and prostate apoptosis response 4 (PAR-4): potential mechanism of apoptosis induction in Alzheimer disease (AD) J. Biol. Chem. 287 25 2012 21384 21395
112. H. Harizi, J.B. Corcuff, and N. Gualde Arachidonic-acid-derived eicosanoids: roles in biology and immunopathology Trends Mol. Med. 14 10 2008 461 469
113. K. Laulagnier, C. Motta, S. Hamdi, S. Roy, F. Fauvelle, J.F. Pageaux, T. Kobayashi, J.P. Salles, B. Perret, C. Bonnerot, and M. Record Mast cell- and dendritic cell-derived exosomes display a specific lipid composition and an unusual membrane organization Biochem. J. 380 Pt 1 2004 161 171
114. S. Beloribi, E. Ristorcelli, G. Breuzard, F. Silvy, J. Bertrand-Michel, E. Beraud, A. Verine, and D. Lombardo Exosomal lipids impact notch signaling and induce death of human pancreatic tumoral SOJ-6 cells PLoS ONE 7 10 2012 e47480
115. S. Beloribi-Djefaflia, C. Siret, and D. Lombardo Exosomal lipids induce human pancreatic tumoral MiaPaCa-2 cells resistance through the CXCR4-SDF-1alpha signaling axis Oncoscience 2 1 2015 15 30
116. L. Zakharova, M. Svetlova, and A.F. Fomina T cell exosomes induce cholesterol accumulation in human monocytes via phosphatidylserine receptor J. Cell. Physiol. 212 1 2007 174 181
117. M. He, J. Crow, M. Roth, Y. Zeng, and A.K. Godwin Integrated immunoisolation and protein analysis of circulating exosomes using microfluidic technology Lab Chip 14 19 2014 3773 3780
118. J.J. Gildea, J.E. Seaton, K.G. Victor, C.M. Reyes, D. Bigler Wang, A.C. Pettigrew, C.E. Courtner, N. Shah, H.T. Tran, R.E. Van Sciver, J.M. Carlson, and R.A. Felder Exosomal transfer from human renal proximal tubule cells to distal tubule and collecting duct cells Clin. Biochem. 15 2014 89 94
119. I. Nazarenko, S. Rana, A. Baumann, J. McAlear, A. Hellwig, M. Trendelenburg, G. Lochnit, K.T. Preissner, and M. Zoller Cell surface tetraspanin Tspan8 contributes to molecular pathways of exosome-induced endothelial cell activation Cancer Res. 70 4 2010 1668 1678
120. D. Skokos, H.G. Botros, C. Demeure, J. Morin, R. Peronet, G. Birkenmeier, S. Boudaly, and S. Mecheri Mast cell-derived exosomes induce phenotypic and functional maturation of dendritic cells and elicit specific immune responses in vivo J. Immunol. 170 6 2003 3037 3045
121. D. Zech, S. Rana, M.W. Buchler, and M. Zoller Tumor-exosomes and leukocyte activation: An ambivalent crosstalk Cell Commun. Signal. 10 1 2012 37
122. E. Segura, C. Nicco, B. Lombard, P. Veron, G. Raposo, F. Batteux, S. Amigorena, and C. Thery ICAM-1 on exosomes from mature dendritic cells is critical for efficient naive T-cell priming Blood 106 1 2005 216 223
123. B. Escudier, T. Dorval, N. Chaput, F. Andre, M.P. Caby, S. Novault, C. Flament, C. Leboulaire, C. Borg, S. Amigorena, C. Boccaccio, C. Bonnerot, O. Dhellin, M. Movassagh, S. Piperno, C. Robert, V. Serra, N. Valente, J.B. Le Pecq, A. Spatz, O. Lantz, T. Tursz, E. Angevin, and L. Zitvogel Vaccination of metastatic melanoma patients with autologous dendritic cell (DC) derived-exosomes: results of the first phase I clinical trial J. Transl. Med. 3 1 2005 10
124. A.N. Kapanidis, N.K. Lee, T.A. Laurence, S. Doose, E. Margeat, and S. Weiss Fluorescence-aided molecule sorting: Analysis of structure and interactions by alternating-laser excitation of single molecules Proc. Natl. Acad. Sci. U. S. A. 101 24 2004 8936 8941