Focus on extracellular vesicles: Physiological role and signalling properties of extracellular membrane vesicles

International Journal of Molecular Sciences

Volumn 17, Issue 2, 2016, Pages

  Iraci, Nunzio ^a   Leonardi, Tommaso ^a,b   Gessler, Florian ^a   Vega, Beatriz ^a   Pluchino, Stefano ^a  

^a UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^b WELLCOME TRUST SANGER INSTITUTE   (United Kingdom)

Author keywords

Drug delivery; Exosomes; Extracellular RNAs; Extracellular vesicles; Intercellular communication; Neuroscience; Signalling pathway; Trafficking

Indexed keywords

BIOLOGICAL MARKER; MICRORNA; PROTEIN; RNA;

ALZHEIMER DISEASE; AMYOTROPHIC LATERAL SCLEROSIS; CENTRAL NERVOUS SYSTEM; EXOSOME; IMMUNE RESPONSE; IMMUNE SYSTEM; IMMUNOMODULATION; MULTIPLE SCLEROSIS; NONHUMAN; PARKINSON DISEASE; PATHOLOGY; PHYSIOLOGY; PRION; PROTEIN SECRETION; REGENERATION; REVIEW; SIGNAL TRANSDUCTION; STRESS; ANIMAL; CELL COMMUNICATION; CELL TRANSFORMATION; DISEASE PREDISPOSITION; DRUG DELIVERY SYSTEM; GENETICS; HUMAN; METABOLISM; TRANSPORT AT THE CELLULAR LEVEL;

ANIMALS; BIOLOGICAL TRANSPORT; CELL COMMUNICATION; CELL TRANSFORMATION, NEOPLASTIC; DISEASE SUSCEPTIBILITY; DRUG DELIVERY SYSTEMS; EXOSOMES; EXTRACELLULAR VESICLES; HUMANS; IMMUNOMODULATION; PROTEINS; RNA; SIGNAL TRANSDUCTION;

EID: 84957586685     PISSN: 16616596     EISSN: 14220067     Source Type: Journal    
DOI: 10.3390/ijms17020171     Document Type: Review

References (275)

1. Gould, S.J., Raposo, G. As we wait: Coping with an imperfect nomenclature for extracellular vesicles. J. Extracell. Vesicles 2013, 2, doi:10.3402/jev.v2i0.20389.
2. Colombo, M., Raposo, G., Thery, C. Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annu. Rev. Cell Dev. Biol. 2014, 30, 255-289.
3. Deatherage, B.L., Cookson, B.T. Membrane vesicle release in bacteria, eukaryotes, and archaea: A conserved yet underappreciated aspect of microbial life. Infect. Immun. 2012, 80, 1948-1957.
4. Kuehn, M.J., Kesty, N.C. Bacterial outer membrane vesicles and the host-pathogen interaction. Genes Dev. 2005, 19, 2645-2655.
5. Johnstone, R.M., Adam, M., Hammond, J.R., Orr, L., Turbide, C. Vesicle formation during reticulocyte maturation. Association of plasma membrane activities with released vesicles (exosomes). J. Biol. Chem. 1987, 262, 9412-9420.
6. Bobrie, A., Colombo, M., Raposo, G., Thery, C. Exosome secretion: Molecular mechanisms and roles in immune responses. Traffic 2011, 12, 1659-1668.
7. Mittelbrunn, M., Gutierrez-Vazquez, C., Villarroya-Beltri, C., Gonzalez, S., Sanchez-Cabo, F., Gonzalez, M.A., Bernad, A., Sanchez-Madrid, F. Unidirectional transfer of microRNA-loaded exosomes from T cells to antigen-presenting cells. Nat. Commun. 2011, 2, doi:10.1038/ncomms1285.
8. Wiley, R.D., Gummuluru, S. Immature dendritic cell-derived exosomes can mediate HIV-1 trans infection. Proc. Natl. Acad. Sci. USA 2006, 103, 738-743.
9. Bukong, T.N., Momen-Heravi, F., Kodys, K., Bala, S., Szabo, G. Exosomes from hepatitis C infected patients transmit HCV infection and contain replication competent viral RNA in complex with Ago2-miR122-HSP90. PLoS Pathog. 2014, 10, e1004424.
10. Longatti, A., Boyd, B., Chisari, F.V. Virion-independent transfer of replication-competent hepatitis C virus RNA between permissive cells. J. Virol. 2015, 89, 2956-2961.
11. Fevrier, B., Vilette, D., Archer, F., Loew, D., Faigle, W., Vidal, M., Laude, H., Raposo, G. Cells release prions in association with exosomes. Proc. Natl. Acad. Sci. USA 2004, 101, 9683-9688.
12. Eder, C. Mechanisms of interleukin-1β release. Immunobiology 2009, 214, 543-553.
13. Li, J., Liu, K., Liu, Y., Xu, Y., Zhang, F., Yang, H., Liu, J., Pan, T., Chen, J., Wu, M., et al. Exosomes mediate the cell-to-cell transmission of IFN-α-induced antiviral activity. Nat. Immunol. 2013, 14, 793-803.
14. Cossetti, C., Iraci, N., Mercer, T.R., Leonardi, T., Alpi, E., Drago, D., Alfaro-Cervello, C., Saini, H.K., Davis, M.P., Schaeffer, J., et al. Extracellular vesicles from neural stem cells transfer IFN-γ via Ifngr1 to activate Stat1 signaling in target cells. Mol. Cell 2014, 56, 193-204.
15. Al-Nedawi, K., Meehan, B., Rak, J. Microvesicles: Messengers and mediators of tumor progression. Cell Cycle 2009, 8, 2014-2018.
16. Raposo, G., Stoorvogel, W. Extracellular vesicles: Exosomes, microvesicles, and friends. J. Cell Biol. 2013, 200, 373-383.
17. Smith, J.A., Leonardi, T., Huang, B., Iraci, N., Vega, B., Pluchino, S. Extracellular vesicles and their synthetic analogues in aging and age-associated brain diseases. Biogerontology 2015, 16, 147-185.
18. Cocucci, E., Racchetti, G., Meldolesi, J. Shedding microvesicles: Artefacts no more. Trends Cell Biol. 2009, 19, 43-51.
19. Kalra, H., Drummen, G.P.C., Mathivanan, S. Focus on extracellular vesicles: An introduction to the next small big thing. Int. J. Mol. Sci. 2016, 17, doi:10.3390/ijms17020170.
20. Kim, D.K., Lee, J., Simpson, R.J., Lotvall, J., Gho, Y.S. EVpedia: A community web resource for prokaryotic and eukaryotic extracellular vesicles research. Semin. Cell Dev. Biol. 2015, 40, 4-7.
21. Kalra, H., Simpson, R.J., Ji, H., Aikawa, E., Altevogt, P., Askenase, P., Bond, V.C., Borras, F.E., Breakefield, X., Budnik, V., et al. Vesiclepedia: A compendium for extracellular vesicles with continuous community annotation. PLoS Biol. 2012, 10, e1001450.
22. Wilkinson, G., Smeeton, N., Skuse, D., Fry, J. Consultation for physical illnesses by patients diagnosed and treated for psychiatric disorders by a general practitioner: 20 year follow up study. BMJ 1988, 297, 776-778.
23. Ratajczak, J., Miekus, K., Kucia, M., Zhang, J., Reca, R., Dvorak, P., Ratajczak, M.Z. Embryonic stem cell-derived microvesicles reprogram hematopoietic progenitors: Evidence for horizontal transfer of mRNA and protein delivery. Leukemia 2006, 20, 847-856.
24. Valadi, H., Ekstrom, K., Bossios, A., Sjostrand, M., Lee, J.J., Lotvall, J.O. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat. Cell Biol. 2007, 9, 654-659.
25. Skog, J., Wurdinger, T., van Rijn, S., Meijer, D.H., Gainche, L., Sena-Esteves, M., Curry, W.T., Jr., Carter, B.S., Krichevsky, A.M., Breakefield, X.O. Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat. Cell Biol. 2008, 10, 1470-1476.
26. Balaj, L., Lessard, R., Dai, L., Cho, Y.J., Pomeroy, S.L., Breakefield, X.O., Skog, J. Tumour microvesicles contain retrotransposon elements and amplified oncogene sequences. Nat. Commun. 2011, 2, doi:10.1038/ncomms1180.
27. Eldh, M., Ekstrom, K., Valadi, H., Sjostrand, M., Olsson, B., Jernas, M., Lotvall, J. Exosomes communicate protective messages during oxidative stress; possible role of exosomal shuttle RNA. PLoS ONE 2010, 5, e15353.
28. Deregibus, M.C., Cantaluppi, V., Calogero, R., Lo Iacono, M., Tetta, C., Biancone, L., Bruno, S., Bussolati, B., Camussi, G. Endothelial progenitor cell derived microvesicles activate an angiogenic program in endothelial cells by a horizontal transfer of mRNA. Blood 2007, 110, 2440-2448.
29. Montecalvo, A., Larregina, A.T., Shufesky, W.J., Stolz, D.B., Sullivan, M.L., Karlsson, J.M., Baty, C.J., Gibson, G.A., Erdos, G., Wang, Z., et al. Mechanism of transfer of functional microRNAs between mouse dendritic cells via exosomes. Blood 2012, 119, 756-766.
30. Pegtel, D.M., Cosmopoulos, K., Thorley-Lawson, D.A., van Eijndhoven, M.A., Hopmans, E.S., Lindenberg, J.L., de Gruijl, T.D., Wurdinger, T., Middeldorp, J.M. Functional delivery of viral miRNAs via exosomes. Proc. Natl. Acad. Sci. USA 2010, 107, 6328-6333.
31. Ismail, N., Wang, Y., Dakhlallah, D., Moldovan, L., Agarwal, K., Batte, K., Shah, P., Wisler, J., Eubank, T.D., Tridandapani, S., et al. Macrophage microvesicles induce macrophage differentiation and miR-223 transfer. Blood 2013, 121, 984-995.
32. Zhuang, G., Wu, X., Jiang, Z., Kasman, I., Yao, J., Guan, Y., Oeh, J., Modrusan, Z., Bais, C., Sampath, D., et al. Tumour-secreted miR-9 promotes endothelial cell migration and angiogenesis by activating the JAK-STAT pathway. EMBO J. 2012, 31, 3513-3523.
33. Zhang, Y., Liu, D., Chen, X., Li, J., Li, L., Bian, Z., Sun, F., Lu, J., Yin, Y., Cai, X., et al. Secreted monocytic miR-150 enhances targeted endothelial cell migration. Mol. Cell 2010, 39, 133-144.
34. Fabbri, M., Paone, A., Calore, F., Galli, R., Gaudio, E., Santhanam, R., Lovat, F., Fadda, P., Mao, C., Nuovo, G.J., et al. MicroRNAs bind to Toll-like receptors to induce prometastatic inflammatory response. Proc. Natl. Acad. Sci. USA 2012, 109, E2110-E2116.
35. Okoye, I.S., Coomes, S.M., Pelly, V.S., Czieso, S., Papayannopoulos, V., Tolmachova, T., Seabra, M.C., Wilson, M.S. MicroRNA-containing T-regulatory-cell-derived exosomes suppress pathogenic T helper 1 cells. Immunity 2014, 41, 89-103.
36. Vojtech, L., Woo, S., Hughes, S., Levy, C., Ballweber, L., Sauteraud, R.P., Strobl, J., Westerberg, K., Gottardo, R., Tewari, M., et al. Exosomes in human semen carry a distinctive repertoire of small non-coding RNAs with potential regulatory functions. Nucleic Acids Res. 2014, 42, 7290-7304.
37. Bellingham, S.A., Coleman, B.M., Hill, A.F. Small RNA deep sequencing reveals a distinct miRNA signature released in exosomes from prion-infected neuronal cells. Nucleic Acids Res. 2012, 40, 10937-10949.
38. Huang, X., Yuan, T., Tschannen, M., Sun, Z., Jacob, H., Du, M., Liang, M., Dittmar, R.L., Liu, Y., Liang, M., et al. Characterization of human plasma-derived exosomal RNAs by deep sequencing. BMC Genom. 2013, 14, 319, doi:10.1186/1471-2164-14-319.
39. Kogure, T., Yan, I.K., Lin, W.L., Patel, T. Extracellular Vesicle-Mediated Transfer of a Novel Long Noncoding RNA TUC339: A Mechanism of Intercellular Signaling in Human Hepatocellular Cancer. Genes Cancer 2013, 4, 261-272.
40. Gezer, U., Ozgur, E., Cetinkaya, M., Isin, M., Dalay, N. Long non-coding RNAs with low expression levels in cells are enriched in secreted exosomes. Cell Biol. Int. 2014, 38, 1076-1079.
41. Takahashi, K., Yan, I.K., Kogure, T., Haga, H., Patel, T. Extracellular vesicle-mediated transfer of long non-coding RNA ROR modulates chemosensitivity in human hepatocellular cancer. FEBS Open Bio 2014, 4, 458-467.
42. Brandimarte, C., Valesini, G., de Berardinis, P.G., Palange, P., Serra, P., Balsano, F. Relapsing polychondritis: A case with anticartilage, anticardiolipin and anticentromere antibodies. Recent. Prog. Med. 1988, 79, 67-69.
43. Lee, T.H., D’Asti, E., Magnus, N., Al-Nedawi, K., Meehan, B., Rak, J. Microvesicles as mediators of intercellular communication in cancer—The emerging science of cellular “debris”. Semin. Immunopathol. 2011, 33, 455-467.
44. Thakur, B.K., Zhang, H., Becker, A., Matei, I., Huang, Y., Costa-Silva, B., Zheng, Y., Hoshino, A., Brazier, H., Xiang, J., et al. Double-stranded DNA in exosomes: A novel biomarker in cancer detection. Cell Res. 2014, 24, 766-769.
45. Olsson, I., Ronquist, G. Nucleic acid association to human prostasomes. Arch. Androl. 1990, 24, 1-10.
46. Tannetta, D., Dragovic, R., Alyahyaei, Z., Southcombe, J. Extracellular vesicles and reproduction-promotion of successful pregnancy. Cell. Mol. Immunol. 2014, 11, 548-563.
47. Ronquist, G. Prostasomes are mediators of intercellular communication: From basic research to clinical implications. J. Intern. Med. 2012, 271, 400-413.
48. Thery, C., Zitvogel, L., Amigorena, S. Exosomes: Composition, biogenesis and function. Nat. Rev. Immunol. 2002, 2, 569-579.
49. Zoller, M. Tetraspanins: Push and pull in suppressing and promoting metastasis. Nat. Rev. Cancer 2009, 9, 40-55.
50. Rana, S., Zoller, M. Exosome target cell selection and the importance of exosomal tetraspanins: A hypothesis. Biochem. Soc. Trans. 2011, 39, 559-562.
51. Tauro, B.J., Greening, D.W., Mathias, R.A., Ji, H., Mathivanan, S., Scott, A.M., Simpson, R.J. Comparison of ultracentrifugation, density gradient separation, and immunoaffinity capture methods for isolating human colon cancer cell line LIM1863-derived exosomes. Methods 2012, 56, 293-304.
52. Colombo, M., Moita, C., van Niel, G., Kowal, J., Vigneron, J., Benaroch, P., Manel, N., Moita, L.F., Thery, C., Raposo, G. Analysis of ESCRT functions in exosome biogenesis, composition and secretion highlights the heterogeneity of extracellular vesicles. J. Cell Sci. 2013, 126, 5553-5565.
53. Tauro, B.J., Greening, D.W., Mathias, R.A., Mathivanan, S., Ji, H., Simpson, R.J. Two distinct populations of exosomes are released from LIM1863 colon carcinoma cell-derived organoids. Mol. Cell. Proteom. 2013, 12, 587-598.
54. Witwer, K.W., Buzas, E.I., Bemis, L.T., Bora, A., Lasser, C., Lotvall, J., Nolte-'t Hoen, E.N., Piper, M.G., Sivaraman, S., Skog, J., et al. Standardization of sample collection, isolation and analysis methods in extracellular vesicle research. J. Extracell. Vesicles 2013, 2, doi:10.3402/jev.v2i0.20360
55. Lancaster, G.I., Febbraio, M.A. Exosome-dependent trafficking of HSP70: A novel secretory pathway for cellular stress proteins. J. Biol. Chem. 2005, 280, 23349-23355.
56. Gastpar, R., Gehrmann, M., Bausero, M.A., Asea, A., Gross, C., Schroeder, J.A., Multhoff, G. Heat shock protein 70 surface-positive tumor exosomes stimulate migratory and cytolytic activity of natural killer cells. Cancer Res. 2005, 65, 5238-5247.
57. Clayton, A., Turkes, A., Navabi, H., Mason, M.D., Tabi, Z. Induction of heat shock proteins in B-cell exosomes. J. Cell Sci. 2005, 118, 3631-3638.
58. Taylor, A.R., Robinson, M.B., Gifondorwa, D.J., Tytell, M., Milligan, C.E. Regulation of heat shock protein 70 release in astrocytes: Role of signaling kinases. Dev. Neurobiol. 2007, 67, 1815-1829.
59. Gupta, S., Knowlton, A.A. HSP60 trafficking in adult cardiac myocytes: Role of the exosomal pathway. Am. J. Physiol. Heart Circ. Physiol. 2007, 292, H3052-H3056.
60. Zhan, R., Leng, X., Liu, X., Wang, X., Gong, J., Yan, L., Wang, L., Wang, Y., Wang, X., Qian, L.J. Heat shock protein 70 is secreted from endothelial cells by a non-classical pathway involving exosomes. Biochem. Biophys. Res. Commun. 2009, 387, 229-233.
61. De Jong, O.G., Verhaar, M.C., Chen, Y., Vader, P., Gremmels, H., Posthuma, G., Schiffelers, R.M., Gucek, M., van Balkom, B.W. Cellular stress conditions are reflected in the protein and RNA content of endothelial cell-derived exosomes. J. Extracell. Vesicles 2012, 1, doi:10.3402/jev.v1i0.18396
62. Beninson, L.A., Fleshner, M. Exosomes: An emerging factor in stress-induced immunomodulation. Semin. Immunol. 2014, 26, 394-401.
63. Kalamvoki, M., Du, T., Roizman, B. Cells infected with herpes simplex virus 1 export to uninfected cells exosomes containing STING, viral mRNAs, and microRNAs. Proc. Natl. Acad. Sci. USA 2014, 111, E4991-E4996.
64. Fevrier, B., Vilette, D., Laude, H., Raposo, G. Exosomes: A bubble ride for prions? Traffic 2005, 6, 10-17.
65. Porto-Carreiro, I., Fevrier, B., Paquet, S., Vilette, D., Raposo, G. Prions and exosomes: From PrPc trafficking to PrPsc propagation. Blood Cells Mol. Dis. 2005, 35, 143-148.
66. Kore, R.A., Abraham, E.C. Inflammatory cytokines, interleukin-1 β and tumor necrosis factor-α, upregulated in glioblastoma multiforme, raise the levels of CRYAB in exosomes secreted by U373 glioma cells. Biochem. Biophys. Res. Commun. 2014, 453, 326-331.
67. Kato, T., Miyaki, S., Ishitobi, H., Nakamura, Y., Nakasa, T., Lotz, M.K., Ochi, M. Exosomes from IL-1β stimulated synovial fibroblasts induce osteoarthritic changes in articular chondrocytes. Arthritis Res. Ther. 2014, 16, doi:10.1186/ar4679.
68. Ekstrom, E.J., Bergenfelz, C., von Bulow, V., Serifler, F., Carlemalm, E., Jonsson, G., Andersson, T., Leandersson, K. WNT5A induces release of exosomes containing pro-angiogenic and immunosuppressive factors from malignant melanoma cells. Mol. Cancer 2014, 13, doi:10.1186/1476-4598-13-88.
69. Kosaka, N., Iguchi, H., Yoshioka, Y., Takeshita, F., Matsuki, Y., Ochiya, T. Secretory mechanisms and intercellular transfer of microRNAs in living cells. J. Biol. Chem. 2010, 285, 17442-17452.
70. Villarroya-Beltri, C., Gutierrez-Vazquez, C., Sanchez-Cabo, F., Perez-Hernandez, D., Vazquez, J., Martin-Cofreces, N., Martinez-Herrera, D.J., Pascual-Montano, A., Mittelbrunn, M., Sanchez-Madrid, F. Sumoylated hnRNPA2B1 controls the sorting of miRNAs into exosomes through binding to specific motifs. Nat. Commun. 2013, 4, doi:10.1038/ncomms3980.
71. Wang, K., Zhang, S., Weber, J., Baxter, D., Galas, D.J. Export of microRNAs and microRNA-protective protein by mammalian cells. Nucleic Acids Res. 2010, 38, 7248-7259.
72. Melo, S.A., Sugimoto, H., O’Connell, J.T., Kato, N., Villanueva, A., Vidal, A., Qiu, L., Vitkin, E., Perelman, L.T., Melo, C.A., et al. Cancer exosomes perform cell-independent microRNA biogenesis and promote tumorigenesis. Cancer Cell 2014, 26, 707-721.
73. Munro, T.P., Magee, R.J., Kidd, G.J., Carson, J.H., Barbarese, E., Smith, L.M., Smith, R. Mutational analysis of a heterogeneous nuclear ribonucleoprotein A2 response element for RNA trafficking. J. Biol. Chem. 1999, 274, 34389-34295.
74. Levesque, K., Halvorsen, M., Abrahamyan, L., Chatel-Chaix, L., Poupon, V., Gordon, H., DesGroseillers, L., Gatignol, A., Mouland, A.J. Trafficking of HIV-1 RNA is mediated by heterogeneous nuclear ribonucleoprotein A2 expression and impacts on viral assembly. Traffic 2006, 7, 1177-1193.
75. Booth, A.M., Fang, Y., Fallon, J.K., Yang, J.M., Hildreth, J.E., Gould, S.J. Exosomes and HIV Gag bud from endosome-like domains of the T cell plasma membrane. J. Cell Biol. 2006, 172, 923-935.
76. Koppers-Lalic, D., Hackenberg, M., Bijnsdorp, I.V., van Eijndhoven, M.A., Sadek, P., Sie, D., Zini, N., Middeldorp, J.M., Ylstra, B., de Menezes, R.X., et al. Nontemplated nucleotide additions distinguish the small RNA composition in cells from exosomes. Cell Rep. 2014, 8, 1649-1658.
77. Squadrito, M.L., Baer, C., Burdet, F., Maderna, C., Gilfillan, G.D., Lyle, R., Ibberson, M., de Palma, M. Endogenous RNAs modulate microRNA sorting to exosomes and transfer to acceptor cells. Cell Rep. 2014, 8, 1432-1446.
78. Bolukbasi, M.F., Mizrak, A., Ozdener, G.B., Madlener, S., Strobel, T., Erkan, E.P., Fan, J.B., Breakefield, X.O., Saydam, O. miR-1289 and “Zipcode”-like Sequence Enrich mRNAs in Microvesicles. Mol. Ther. Nucleic Acids 2012, 1, e10.
79. Batagov, A.O., Kuznetsov, V.A., Kurochkin, I.V. Identification of nucleotide patterns enriched in secreted RNAs as putative cis-acting elements targeting them to exosome nano-vesicles. BMC Genom. 2011, 12, doi:10.1186/1471-2164-12-S3-S18.
80. Szostak, N., Royo, F., Rybarczyk, A., Szachniuk, M., Blazewicz, J., del Sol, A., Falcon-Perez, J.M. Sorting signal targeting mRNA into hepatic extracellular vesicles. RNA Biol. 2014, 11, 836-844.
81. Villarroya-Beltri, C., Baixauli, F., Gutierrez-Vazquez, C., Sanchez-Madrid, F., Mittelbrunn, M. Sorting it out: Regulation of exosome loading. Semin. Cancer Biol. 2014, 28, 3-13.
82. Moreno-Gonzalo, O., Villarroya-Beltri, C., Sanchez-Madrid, F. Post-translational modifications of exosomal proteins. Front. Immunol. 2014, 5, doi:10.3389/fimmu.2014.00383.
83. Henne, W.M., Buchkovich, N.J., Emr, S.D. The ESCRT pathway. Dev. Cell 2011, 21, 77-91.
84. Blot, V., Perugi, F., Gay, B., Prevost, M.C., Briant, L., Tangy, F., Abriel, H., Staub, O., Dokhelar, M.C., Pique, C. Nedd4.1-mediated ubiquitination and subsequent recruitment of Tsg101 ensure HTLV-1 Gag trafficking towards the multivesicular body pathway prior to virus budding. J. Cell Sci. 2004, 117, 2357-2367.
85. Verweij, F.J., van Eijndhoven, M.A., Hopmans, E.S., Vendrig, T., Wurdinger, T., Cahir-McFarland, E., Kieff, E., Geerts, D., van der Kant, R., Neefjes, J., et al. LMP1 association with CD63 in endosomes and secretion via exosomes limits constitutive NF-kappaB activation. EMBO J. 2011, 30, 2115-2129.
86. Shen, B., Wu, N., Yang, J.M., Gould, S.J. Protein targeting to exosomes/microvesicles by plasma membrane anchors. J. Biol. Chem. 2011, 286, 14383-14395.
87. Yuyama, K., Sun, H., Mitsutake, S., Igarashi, Y. Sphingolipid-modulated exosome secretion promotes clearance of amyloid-β by microglia. J. Biol. Chem. 2012, 287, 10977-10989.
88. Trams, E.G., Lauter, C.J., Salem, N., Jr., Heine, U. Exfoliation of membrane ecto-enzymes in the form of micro-vesicles. Biochim. Biophys. Acta 1981, 645, 63-70.
89. Stegmayr, B., Ronquist, G. Promotive effect on human sperm progressive motility by prostasomes. Urol. Res. 1982, 10, 253-257.
90. Harding, C., Heuser, J., Stahl, P. Receptor-mediated endocytosis of transferrin and recycling of the transferrin receptor in rat reticulocytes. J. Cell Biol. 1983, 97, 329-339.
91. Pan, B.T., Johnstone, R.M. Fate of the transferrin receptor during maturation of sheep reticulocytes in vitro: Selective externalization of the receptor. Cell 1983, 33, 967-978.
92. Cossetti, C., Smith, J.A., Iraci, N., Leonardi, T., Alfaro-Cervello, C., Pluchino, S. Extracellular membrane vesicles and immune regulation in the brain. Front. Physiol. 2012, 3, doi:10.3389/fphys.2012.00117.
93. Raposo, G., Nijman, H.W., Stoorvogel, W., Liejendekker, R., Harding, C.V., Melief, C.J., Geuze, H.J. B lymphocytes secrete antigen-presenting vesicles. J. Exp. Med. 1996, 183, 1161-1172.
94. Denzer, K., van Eijk, M., Kleijmeer, M.J., Jakobson, E., de Groot, C., Geuze, H.J. Follicular dendritic cells carry MHC class II-expressing microvesicles at their surface. J. Immunol. 2000, 165, 1259-1265.
95. Robbins, P.D., Morelli, A.E. Regulation of immune responses by extracellular vesicles. Nat. Rev. Immunol. 2014, 14, 195-208.
96. Vincent-Schneider, H., Stumptner-Cuvelette, P., Lankar, D., Pain, S., Raposo, G., Benaroch, P., Bonnerot, C. Exosomes bearing HLA-DR1 molecules need dendritic cells to efficiently stimulate specific T cells. Int. Immunol. 2002, 14, 713-722.
97. Mallegol, J., van Niel, G., Lebreton, C., Lepelletier, Y., Candalh, C., Dugave, C., Heath, J.K., Raposo, G., Cerf-Bensussan, N., Heyman, M. T84-intestinal epithelial exosomes bear MHC class II/peptide complexes potentiating antigen presentation by dendritic cells. Gastroenterology 2007, 132, 1866-1876.
98. Morelli, A.E., Larregina, A.T., Shufesky, W.J., Sullivan, M.L., Stolz, D.B., Papworth, G.D., Zahorchak, A.F., Logar, A.J., Wang, Z., Watkins, S.C., et al. Endocytosis, intracellular sorting, and processing of exosomes by dendritic cells. Blood 2004, 104, 3257-3266.
99. Thery, C., Duban, L., Segura, E., Veron, P., Lantz, O., Amigorena, S. Indirect activation of naive CD4+ T cells by dendritic cell-derived exosomes. Nat. Immunol. 2002, 3, 1156-1162.
100. Bedford, P., Garner, K., Knight, S.C. MHC class II molecules transferred between allogeneic dendritic cells stimulate primary mixed leukocyte reactions. Int. Immunol. 1999, 11, 1739-1744.
101. Patel, D.M., Arnold, P.Y., White, G.A., Nardella, J.P., Mannie, M.D. Class II MHC/peptide complexes are released from APC and are acquired by T cell responders during specific antigen recognition. J. Immunol. 1999, 163, 5201-5210.
102. Thery, C., Regnault, A., Garin, J., Wolfers, J., Zitvogel, L., Ricciardi-Castagnoli, P., Raposo, G., Amigorena, S. Molecular characterization of dendritic cell-derived exosomes. Selective accumulation of the heat shock protein hsc73. J. Cell Biol. 1999, 147, 599-610.
103. Zitvogel, L., Regnault, A., Lozier, A., Wolfers, J., Flament, C., Tenza, D., Ricciardi-Castagnoli, P., Raposo, G., Amigorena, S. Eradication of established murine tumors using a novel cell-free vaccine: Dendritic cell-derived exosomes. Nat. Med. 1998, 4, 594-600.
104. Segura, E., Guerin, C., Hogg, N., Amigorena, S., Thery, C. CD8+ dendritic cells use LFA-1 to capture MHC-peptide complexes from exosomes in vivo. J. Immunol. 2007, 179, 1489-1496.
105. Nolte-'t Hoen, E.N., Buschow, S.I., Anderton, S.M., Stoorvogel, W., Wauben, M.H. Activated T cells recruit exosomes secreted by dendritic cells via LFA-1. Blood 2009, 113, 1977-1981.
106. Monks, C.R., Freiberg, B.A., Kupfer, H., Sciaky, N., Kupfer, A. Three-dimensional segregation of supramolecular activation clusters in T cells. Nature 1998, 395, 82-86.
107. Bhatnagar, S., Shinagawa, K., Castellino, F.J., Schorey, J.S. Exosomes released from macrophages infected with intracellular pathogens stimulate a proinflammatory response in vitro and in vivo. Blood 2007, 110, 3234-3244.
108. Bhatnagar, S., Schorey, J.S. Exosomes released from infected macrophages contain Mycobacterium avium glycopeptidolipids and are proinflammatory. J. Biol. Chem. 2007, 282, 25779-25789.
109. Qu, Y., Franchi, L., Nunez, G., Dubyak, G.R. Nonclassical IL-1β secretion stimulated by P2X7 receptors is dependent on inflammasome activation and correlated with exosome release in murine macrophages. J. Immunol. 2007, 179, 1913-1925.
110. Ramachandra, L., Qu, Y., Wang, Y., Lewis, C.J., Cobb, B.A., Takatsu, K., Boom, W.H., Dubyak, G.R., Harding, C.V. Mycobacterium tuberculosis synergizes with ATP to induce release of microvesicles and exosomes containing major histocompatibility complex class II molecules capable of antigen presentation. Infect. Immun. 2010, 78, 5116-5125.
111. Iero, M., Valenti, R., Huber, V., Filipazzi, P., Parmiani, G., Fais, S., Rivoltini, L. Tumour-released exosomes and their implications in cancer immunity. Cell Death Differ. 2008, 15, 80-88.
112. Zhang, H.G., Grizzle, W.E. Exosomes and cancer: A newly described pathway of immune suppression. Clin. Cancer Res. 2011, 17, 959-964.
113. Wieckowski, E., Whiteside, T.L. Human tumor-derived vs dendritic cell-derived exosomes have distinct biologic roles and molecular profiles. Immunol. Res. 2006, 36, 247-254.
114. Clayton, A., Mitchell, J.P., Court, J., Mason, M.D., Tabi, Z. Human tumor-derived exosomes selectively impair lymphocyte responses to interleukin-2. Cancer Res. 2007, 67, 7458-7466.
115. Andreola, G., Rivoltini, L., Castelli, C., Huber, V., Perego, P., Deho, P., Squarcina, P., Accornero, P., Lozupone, F., Lugini, L., et al. Induction of lymphocyte apoptosis by tumor cell secretion of FasL-bearing microvesicles. J. Exp. Med. 2002, 195, 1303-1316.
116. Huber, V., Fais, S., Iero, M., Lugini, L., Canese, P., Squarcina, P., Zaccheddu, A., Colone, M., Arancia, G., Gentile, M., et al. Human colorectal cancer cells induce T-cell death through release of proapoptotic microvesicles: Role in immune escape. Gastroenterology 2005, 128, 1796-1804.
117. Szajnik, M., Czystowska, M., Szczepanski, M.J., Mandapathil, M., Whiteside, T.L. Tumor-derived microvesicles induce, expand and up-regulate biological activities of human regulatory T cells (Treg). PLoS ONE 2010, 5, e11469.
118. Zeelenberg, I.S., Ostrowski, M., Krumeich, S., Bobrie, A., Jancic, C., Boissonnas, A., Delcayre, A., le Pecq, J.B., Combadiere, B., Amigorena, S., et al. Targeting tumor antigens to secreted membrane vesicles in vivo induces efficient antitumor immune responses. Cancer Res. 2008, 68, 1228-1235.
119. Valenti, R., Huber, V., Filipazzi, P., Pilla, L., Sovena, G., Villa, A., Corbelli, A., Fais, S., Parmiani, G., Rivoltini, L. Human tumor-released microvesicles promote the differentiation of myeloid cells with transforming growth factor-β-mediated suppressive activity on T lymphocytes. Cancer Res. 2006, 66, 9290-9298.
120. Liu, C., Yu, S., Zinn, K., Wang, J., Zhang, L., Jia, Y., Kappes, J.C., Barnes, S., Kimberly, R.P., Grizzle, W.E., et al. Murine mammary carcinoma exosomes promote tumor growth by suppression of NK cell function. J. Immunol. 2006, 176, 1375-1385.
121. Greening, D.W., Gopal, S.K., Xu, R., Simpson, R.J., Chen, W. Exosomes and their roles in immune regulation and cancer. Semin. Cell Dev. Biol. 2015, 40, 72-81.
122. Hedlund, M., Stenqvist, A.C., Nagaeva, O., Kjellberg, L., Wulff, M., Baranov, V., Mincheva-Nilsson, L. Human placenta expresses and secretes NKG2D ligands via exosomes that down-modulate the cognate receptor expression: Evidence for immunosuppressive function. J. Immunol. 2009, 183, 340-351.
123. Van Niel, G., Raposo, G., Candalh, C., Boussac, M., Hershberg, R., Cerf-Bensussan, N., Heyman, M. Intestinal epithelial cells secrete exosome-like vesicles. Gastroenterology 2001, 121, 337-349.
124. Van Niel, G., Mallegol, J., Bevilacqua, C., Candalh, C., Brugiere, S., Tomaskovic-Crook, E., Heath, J.K., Cerf-Bensussan, N., Heyman, M. Intestinal epithelial exosomes carry MHC class II/peptides able to inform the immune system in mice. Gut 2003, 52, 1690-1697.
125. Qazi, K.R., Torregrosa Paredes, P., Dahlberg, B., Grunewald, J., Eklund, A., Gabrielsson, S. Proinflammatory exosomes in bronchoalveolar lavage fluid of patients with sarcoidosis. Thorax 2010, 65, 1016-1024.
126. Prado, N., Marazuela, E.G., Segura, E., Fernandez-Garcia, H., Villalba, M., Thery, C., Rodriguez, R., Batanero, E. Exosomes from bronchoalveolar fluid of tolerized mice prevent allergic reaction. J. Immunol. 2008, 181, 1519-1525.
127. De Carvalho, J.V., de Castro, R.O., da Silva, E.Z., Silveira, P.P., da Silva-Januario, M.E., Arruda, E., Jamur, M.C., Oliver, C., Aguiar, R.S., daSilva, L.L. Nef neutralizes the ability of exosomes from CD4+ T cells to act as decoys during HIV-1 infection. PLoS ONE 2014, 9, e113691.
128. Raivich, G., Banati, R. Brain microglia and blood-derived macrophages: Molecular profiles and functional roles in multiple sclerosis and animal models of autoimmune demyelinating disease. Brain Res. Brain Res. Rev. 2004, 46, 261-281.
129. Streit, W.J., Kincaid-Colton, C.A. The brain’s immune system. Sci. Am. 1995, 273, 58-61.
130. Kettenmann, H., Hanisch, U.K., Noda, M., Verkhratsky, A. Physiology of microglia. Physiol. Rev. 2011, 91, 461-553.
131. Tremblay, M.E., Stevens, B., Sierra, A., Wake, H., Bessis, A., Nimmerjahn, A. The role of microglia in the healthy brain. J. Neurosci. 2011, 31, 16064-16069.
132. Aloisi, F., Ambrosini, E., Columba-Cabezas, S., Magliozzi, R., Serafini, B. Intracerebral regulation of immune responses. Ann. Med. 2001, 33, 510-515.
133. Kettenmann, H. Neuroscience: The brain’s garbage men. Nature 2007, 446, 987-989.
134. Yang, I., Han, S.J., Kaur, G., Crane, C., Parsa, A.T. The role of microglia in central nervous system immunity and glioma immunology. J. Clin. Neurosci. 2010, 17, 6-10.
135. Potolicchio, I., Carven, G.J., Xu, X., Stipp, C., Riese, R.J., Stern, L.J., Santambrogio, L. Proteomic analysis of microglia-derived exosomes: Metabolic role of the aminopeptidase CD13 in neuropeptide catabolism. J. Immunol. 2005, 175, 2237-2243.
136. Bianco, F., Pravettoni, E., Colombo, A., Schenk, U., Moller, T., Matteoli, M., Verderio, C. Astrocyte-derived ATP induces vesicle shedding and IL-1 β release from microglia. J. Immunol. 2005, 174, 7268-7277.
137. Bianco, F., Perrotta, C., Novellino, L., Francolini, M., Riganti, L., Menna, E., Saglietti, L., Schuchman, E.H., Furlan, R., et al. Acid sphingomyelinase activity triggers microparticle release from glial cells. EMBO J. 2009, 28, 1043-1054.
138. Verderio, C., Muzio, L., Turola, E., Bergami, A., Novellino, L., Ruffini, F., Riganti, L., Corradini, I., Francolini, M., Garzetti, L., et al. Myeloid microvesicles are a marker and therapeutic target for neuroinflammation. Ann. Neurol. 2012, 72, 610-624.
139. Kramer-Albers, E.M., Bretz, N., Tenzer, S., Winterstein, C., Mobius, W., Berger, H., Nave, K.A., Schild, H., Trotter, J. Oligodendrocytes secrete exosomes containing major myelin and stress-protective proteins: Trophic support for axons? Proteom. Clin. Appl. 2007, 1, 1446-1461.
140. Bakhti, M., Winter, C., Simons, M. Inhibition of myelin membrane sheath formation by oligodendrocyte-derived exosome-like vesicles. J. Biol. Chem. 2011, 286, 787-796.
141. Lopez-Verrilli, M.A., Picou, F., Court, F.A. Schwann cell-derived exosomes enhance axonal regeneration in the peripheral nervous system. Glia 2013, 61, 1795-1806.
142. Fitzner, D., Schnaars, M., van Rossum, D., Krishnamoorthy, G., Dibaj, P., Bakhti, M., Regen, T., Hanisch, U.K., Simons, M. Selective transfer of exosomes from oligodendrocytes to microglia by macropinocytosis. J. Cell Sci. 2011, 124, 447-458.
143. Antonucci, F., Turola, E., Riganti, L., Caleo, M., Gabrielli, M., Perrotta, C., Novellino, L., Clementi, E., Giussani, P., Viani, P., et al. Microvesicles released from microglia stimulate synaptic activity via enhanced sphingolipid metabolism. EMBO J. 2012, 31, 1231-1240.
144. Wang, S., Cesca, F., Loers, G., Schweizer, M., Buck, F., Benfenati, F., Schachner, M., Kleene, R. Synapsin I is an oligomannose-carrying glycoprotein, acts as an oligomannose-binding lectin, and promotes neurite outgrowth and neuronal survival when released via glia-derived exosomes. J. Neurosci. 2011, 31, 7275-7290.
145. Schiera, G., Proia, P., Alberti, C., Mineo, M., Savettieri, G., di Liegro, I. Neurons produce FGF2 and VEGF and secrete them at least in part by shedding extracellular vesicles. J. Cell. Mol. Med. 2007, 11, 1384-1394.
146. Lachenal, G., Pernet-Gallay, K., Chivet, M., Hemming, F.J., Belly, A., Bodon, G., Blot, B., Haase, G., Goldberg, Y., Sadoul, R. Release of exosomes from differentiated neurons and its regulation by synaptic glutamatergic activity. Mol. Cell. Neurosci. 2011, 46, 409-418.
147. Korkut, C., Ataman, B., Ramachandran, P., Ashley, J., Barria, R., Gherbesi, N., Budnik, V. Trans-synaptic transmission of vesicular Wnt signals through Evi/Wntless. Cell 2009, 139, 393-404.
148. Gross, J.C., Chaudhary, V., Bartscherer, K., Boutros, M. Active Wnt proteins are secreted on exosomes. Nat. Cell Biol. 2012, 14, 1036-1045.
149. Sheldon, H., Heikamp, E., Turley, H., Dragovic, R., Thomas, P., Oon, C.E., Leek, R., Edelmann, M., Kessler, B., Sainson, R.C., et al. New mechanism for Notch signaling to endothelium at a distance by δ-like 4 incorporation into exosomes. Blood 2010, 116, 2385-2394.
150. Panakova, D., Sprong, H., Marois, E., Thiele, C., Eaton, S. Lipoprotein particles are required for Hedgehog and Wingless signalling. Nature 2005, 435, 58-65.
151. Peinado, H., Aleckovic, M., Lavotshkin, S., Matei, I., Costa-Silva, B., Moreno-Bueno, G., Hergueta-Redondo, M., Williams, C., Garcia-Santos, G., Ghajar, C., et al. Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET. Nat. Med. 2012, 18, 883-891.
152. Costa-Silva, B., Aiello, N.M., Ocean, A.J., Singh, S., Zhang, H., Thakur, B.K., Becker, A., Hoshino, A., Mark, M.T., Molina, H., et al. Pancreatic cancer exosomes initiate pre-metastatic niche formation in the liver. Nat. Cell Biol. 2015, 17, 816-826.
153. Luga, V., Zhang, L., Viloria-Petit, A.M., Ogunjimi, A.A., Inanlou, M.R., Chiu, E., Buchanan, M., Hosein, A.N., Basik, M., Wrana, J.L. Exosomes mediate stromal mobilization of autocrine Wnt-PCP signaling in breast cancer cell migration. Cell 2012, 151, 1542-1556.
154. Yeh, Y.Y., Ozer, H.G., Lehman, A.M., Maddocks, K., Yu, L., Johnson, A.J., Byrd, J.C. Characterization of CLL exosomes reveals a distinct microRNA signature and enhanced secretion by activation of BCR signaling. Blood 2015, 125, 3297-3305.
155. Boelens, M.C., Wu, T.J., Nabet, B.Y., Xu, B., Qiu, Y., Yoon, T., Azzam, D.J., Twyman-Saint Victor, C., Wiemann, B.Z., Ishwaran, H., et al. Exosome transfer from stromal to breast cancer cells regulates therapy resistance pathways. Cell 2014, 159, 499-513.
156. Ciardiello, C., Cavallini, L., Spinelli, C., Yang, J., Reis-Sobreiro, M., de Candia, P., Minciacchi, V.R., di Vizio, D. Focus on extracellular vesicles: New frontiers of cell-to-cell communication in cancer. Int. J. Mol. Sci. 2016, 17, doi:10.3390/ijms17020175.
157. Camussi, G., Deregibus, M.C., Bruno, S., Grange, C., Fonsato, V., Tetta, C. Exosome/microvesicle-mediated epigenetic reprogramming of cells. Am. J. Cancer Res. 2011, 1, 98-110.
158. Mack, M., Kleinschmidt, A., Bruhl, H., Klier, C., Nelson, P.J., Cihak, J., Plachy, J., Stangassinger, M., Erfle, V., Schlondorff, D. Transfer of the chemokine receptor CCR5 between cells by membrane-derived microparticles: A mechanism for cellular human immunodeficiency virus 1 infection. Nat. Med. 2000, 6, 769-775.
159. Ross, C.A., Poirier, M.A. Opinion: What is the role of protein aggregation in neurodegeneration? Nat. Rev. Mol. Cell Biol. 2005, 6, 891-898.
160. Bellingham, S.A., Guo, B.B., Coleman, B.M., Hill, A.F. Exosomes: Vehicles for the transfer of toxic proteins associated with neurodegenerative diseases? Front. Physiol. 2012, 3, doi:10.3389/fphys.2012.00124.
161. Emmanouilidou, E., Melachroinou, K., Roumeliotis, T., Garbis, S.D., Ntzouni, M., Margaritis, L.H., Stefanis, L., Vekrellis, K. Cell-produced α-synuclein is secreted in a calcium-dependent manner by exosomes and impacts neuronal survival. J. Neurosci. 2010, 30, 6838-6851.
162. Vella, L.J., Sharples, R.A., Lawson, V.A., Masters, C.L., Cappai, R., Hill, A.F. Packaging of prions into exosomes is associated with a novel pathway of PrP processing. J. Pathol. 2007, 211, 582-590.
163. Ghidoni, R., Benussi, L., Binetti, G. Exosomes: The Trojan horses of neurodegeneration. Med. Hypotheses 2008, 70, 1226-1227.
164. Peralta, O.A., Eyestone, W.H. Quantitative and qualitative analysis of cellular prion protein (PrPC) expression in bovine somatic tissues. Prion 2009, 3, 161-170.
165. Jucker, M., Walker, L.C. Self-propagation of pathogenic protein aggregates in neurodegenerative diseases. Nature 2013, 501, 45-51.
166. Mabbott, N.A., MacPherson, G.G. Prions and their lethal journey to the brain. Nat. Rev. Microbiol. 2006, 4, 201-211.
167. Gousset, K., Schiff, E., Langevin, C., Marijanovic, Z., Caputo, A., Browman, D.T., Chenouard, N., de Chaumont, F., Martino, A., Enninga, J., et al. Prions hijack tunnelling nanotubes for intercellular spread. Nat. Cell Biol. 2009, 11, 328-336.
168. Schneider, A., Simons, M. Exosomes: Vesicular carriers for intercellular communication in neurodegenerative disorders. Cell Tissue Res. 2013, 352, 33-47.
169. Godsave, S.F., Wille, H., Kujala, P., Latawiec, D., DeArmond, S.J., Serban, A., Prusiner, S.B., Peters, P.J. Cryo-immunogold electron microscopy for prions: Toward identification of a conversion site. J. Neurosci. 2008, 28, 12489-12499.
170. Marijanovic, Z., Caputo, A., Campana, V., Zurzolo, C. Identification of an intracellular site of prion conversion. PLoS Pathog. 2009, 5, e1000426.
171. Avramopoulos, D. Genetics of Alzheimer’s disease: Recent advances. Genome Med. 2009, 1, doi:10.1186/gm34.
172. Murphy, M.P., LeVine, H. Alzheimer’s disease and the amyloid-β peptide. J. Alzheimers Dis. 2010, 19, 311-323.
173. Avila, J., Lucas, J.J., Perez, M., Hernandez, F. Role of tau protein in both physiological and pathological conditions. Physiol. Rev. 2004, 84, 361-384.
174. Rajendran, L., Honsho, M., Zahn, T.R., Keller, P., Geiger, K.D., Verkade, P., Simons, K. Alzheimer’s disease β-amyloid peptides are released in association with exosomes. Proc. Natl. Acad. Sci. USA 2006, 103, 11172-11177.
175. Saman, S., Kim, W., Raya, M., Visnick, Y., Miro, S., Saman, S., Jackson, B., McKee, A.C., Alvarez, V.E., Lee, N.C., et al. Exosome-associated tau is secreted in tauopathy models and is selectively phosphorylated in cerebrospinal fluid in early Alzheimer disease. J. Biol. Chem. 2012, 287, 3842-3849.
176. Guo, J.L., Lee, V.M. Seeding of normal Tau by pathological Tau conformers drives pathogenesis of Alzheimer-like tangles. J. Biol. Chem. 2011, 286, 15317-15331.
177. Clavaguera, F., Bolmont, T., Crowther, R.A., Abramowski, D., Frank, S., Probst, A., Fraser, G., Stalder, A.K., Beibel, M., Staufenbiel, M., et al. Transmission and spreading of tauopathy in transgenic mouse brain. Nat. Cell Biol. 2009, 11, 909-913.
178. Ravits, J.M., La Spada A.R. ALS motor phenotype heterogeneity, focality, and spread: Deconstructing motor neuron degeneration. Neurology 2009, 73, 805-811.
179. Haidet-Phillips, A.M., Hester, M.E., Miranda, C.J., Meyer, K., Braun, L., Frakes, A., Song, S., Likhite, S., Murtha, M.J., Foust, K.D., et al. Astrocytes from familial and sporadic ALS patients are toxic to motor neurons. Nat. Biotechnol. 2011, 29, 824-828.
180. Grad, L.I., Yerbury, J.J., Turner, B.J., Guest, W.C., Pokrishevsky, E., O'Neill, M.A., Yanai, A., Silverman, J.M., Zeineddine, R., Corcoran, L., et al. Intercellular propagated misfolding of wild-type Cu/Zn superoxide dismutase occurs via exosome-dependent and -independent mechanisms. Proc. Natl. Acad. Sci. USA 2014, 111, 3620-3625.
181. Gomes, C., Keller, S., Altevogt, P., Costa, J. Evidence for secretion of Cu,Zn superoxide dismutase via exosomes from a cell model of amyotrophic lateral sclerosis. Neurosci. Lett. 2007, 428, 43-46.
182. Compston, A., Coles, A. Multiple sclerosis. Lancet 2008, 372, 1502-1517.
183. Saenz-Cuesta, M., Osorio-Querejeta, I., Otaegui, D. Extracellular vesicles in multiple sclerosis: what are they telling us? Front. Cell. Neurosci. 2014, 8, doi:10.3389/fncel.2014.00100.
184. Minagar, A., Jy, W., Jimenez, J.J., Sheremata, W.A., Mauro, L.M., Mao, W.W., Horstman, L.L., Ahn, Y.S. Elevated plasma endothelial microparticles in multiple sclerosis. Neurology 2001, 56, 1319-1324.
185. Sbai, O., Ould-Yahoui, A., Ferhat, L., Gueye, Y., Bernard, A., Charrat, E., Mehanna, A., Risso, J.J., Chauvin, J.P., Fenouillet, E., et al. Differential vesicular distribution and trafficking of MMP-2, MMP-9, and their inhibitors in astrocytes. Glia 2010, 58, 344-366.
186. Jy, W., Minagar, A., Jimenez, J.J., Sheremata, W.A., Mauro, L.M., Horstman, L.L., Bidot, C., Ahn, Y.S. Endothelial microparticles (EMP) bind and activate monocytes: Elevated EMP-monocyte conjugates in multiple sclerosis. Front. Biosci. 2004, 9, 3137-3144.
187. Sheremata, W.A., Jy, W., Delgado, S., Minagar, A., McLarty, J., Ahn, Y. Interferon-β1a reduces plasma CD31+ endothelial microparticles (CD31+EMP) in multiple sclerosis. J. Neuroinflamm. 2006, 3, doi:10.1186/1742-2094-3-23.
188. Siegel, S.R., Mackenzie, J., Chaplin, G., Jablonski, N.G., Griffiths, L. Circulating microRNAs involved in multiple sclerosis. Mol. Biol. Rep. 2012, 39, 6219-6225.
189. Gatson, N.N., Williams, J.L., Powell, N.D., McClain, M.A., Hennon, T.R., Robbins, P.D., Whitacre, C.C. Induction of pregnancy during established EAE halts progression of CNS autoimmune injury via pregnancy-specific serum factors. J. Neuroimmunol. 2011, 230, 105-113.
190. Williams, J.L., Gatson, N.N., Smith, K.M., Almad, A., McTigue, D.M., Whitacre, C.C. Serum exosomes in pregnancy-associated immune modulation and neuroprotection during CNS autoimmunity. Clin. Immunol. 2013, 149, 236-243.
191. Yu, L., Yang, F., Jiang, L., Chen, Y., Wang, K., Xu, F., Wei, Y., Cao, X., Wang, J., Cai, Z. Exosomes with membrane-associated TGF-β1 from gene-modified dendritic cells inhibit murine EAE independently of MHC restriction. Eur. J. Immunol. 2013, 43, 2461-2472.
192. Davis, S., Lees, K., Donnan, G. Treating the acute stroke patient as an emergency: Current practices and future opportunities. Int. J. Clin. Pract. 2006, 60, 399-407.
193. Butcher, K., Parsons, M., Baird, T., Barber, A., Donnan, G., Desmond, P., Tress, B., Davis, S. Perfusion thresholds in acute stroke thrombolysis. Stroke 2003, 34, 2159-2164.
194. Reed, S.D., Cramer, S.C., Blough, D.K., Meyer, K., Jarvik, J.G. Treatment with tissue plasminogen activator and inpatient mortality rates for patients with ischemic stroke treated in community hospitals. Stroke 2001, 32, 1832-1840.
195. Majid, A. Neuroprotection in stroke: Past, present, and future. ISRN Neurol. 2014, 2014, doi:10.1155/2014/515716.
196. Anderson, H.C., Garimella, R., Tague, S.E. The role of matrix vesicles in growth plate development and biomineralization. Front. Biosci. 2005, 10, 822-837.
197. New, S.E., Goettsch, C., Aikawa, M., Marchini, J.F., Shibasaki, M., Yabusaki, K., Libby, P., Shanahan, C.M., Croce, K., Aikawa, E. Macrophage-derived matrix vesicles: An alternative novel mechanism for microcalcification in atherosclerotic plaques. Circ. Res. 2013, 113, 72-77.
198. New, S.E., Aikawa, E. Role of extracellular vesicles in de novo mineralization: An additional novel mechanism of cardiovascular calcification. Arterioscler. Thromb. Vasc. Biol. 2013, 33, 1753-1758.
199. Hutcheson, J.D., Goettsch, C., Pham, T., Iwashita, M., Aikawa, M., Singh, S.A., Aikawa, E. Enrichment of calcifying extracellular vesicles using density-based ultracentrifugation protocol. J. Extracell. Vesicles 2014, 3, doi:10.3402/jev.v3.25129.
200. Huang, J., Choudhri, T.F., Winfree, C.J., McTaggart, R.A., Kiss, S., Mocco, J., Kim, L.J., Protopsaltis, T.S., Zhang, Y., Pinsky, D.J., et al. Postischemic cerebrovascular E-selectin expression mediates tissue injury in murine stroke. Stroke 2000, 31, 3047-3053.
201. Cherian, P., Hankey, G.J., Eikelboom, J.W., Thom, J., Baker, R.I., McQuillan, A., Staton, J., Yi, Q. Endothelial and platelet activation in acute ischemic stroke and its etiological subtypes. Stroke 2003, 34, 2132-2137.
202. Lee, S.T., Chu, K., Jung, K.H., Kim, J.M., Moon, H.J., Bahn, J.J., Im, W.S., Sunwoo, J., Moon, J., Kim, M., et al. Circulating CD62E+ microparticles and cardiovascular outcomes. PLoS ONE 2012, 7, e35713.
203. Jung, K.H., Chu, K., Lee, S.T., Park, H.K., Bahn, J.J., Kim, D.H., Kim, J.H., Kim, M., Kun Lee, S., Roh, J.K. Circulating endothelial microparticles as a marker of cerebrovascular disease. Ann. Neurol. 2009, 66, 191-199.
204. Martino, G., Pluchino, S. The therapeutic potential of neural stem cells. Nat. Rev. Neurosci. 2006, 7, 395-406.
205. Lee, S.T., Chu, K., Jung, K.H., Kim, S.J., Kim, D.H., Kang, K.M., Hong, N.H., Kim, J.H., Ban, J.J., Park, H.K., et al. Anti-inflammatory mechanism of intravascular neural stem cell transplantation in haemorrhagic stroke. Brain 2008, 131, 616-629.
206. Bacigaluppi, M., Pluchino, S., Peruzzotti-Jametti, L., Kilic, E., Kilic, U., Salani, G., Brambilla, E., West, M.J., Comi, G., Martino, G., et al. Delayed post-ischaemic neuroprotection following systemic neural stem cell transplantation involves multiple mechanisms. Brain 2009, 132, 2239-2251.
207. Pluchino, S., Quattrini, A., Brambilla, E., Gritti, A., Salani, G., Dina, G., Galli, R., Del Carro, U., Amadio, S., Bergami, A., et al. Injection of adult neurospheres induces recovery in a chronic model of multiple sclerosis. Nature 2003, 422, 688-694.
208. Pluchino, S., Zanotti, L., Rossi, B., Brambilla, E., Ottoboni, L., Salani, G., Martinello, M., Cattalini, A., Bergami, A., Furlan, R., et al. Neurosphere-derived multipotent precursors promote neuroprotection by an immunomodulatory mechanism. Nature 2005, 436, 266-271.
209. Aharonowiz, M., Einstein, O., Fainstein, N., Lassmann, H., Reubinoff, B., Ben-Hur, T. Neuroprotective effect of transplanted human embryonic stem cell-derived neural precursors in an animal model of multiple sclerosis. PLoS ONE 2008, 3, e3145.
210. Pluchino, S., Gritti, A., Blezer, E., Amadio, S., Brambilla, E., Borsellino, G., Cossetti, C., Del Carro, U., Comi, G., t Hart, B., et al. Human neural stem cells ameliorate autoimmune encephalomyelitis in non-human primates. Ann. Neurol. 2009, 66, 343-354.
211. Pluchino, S., Zanotti, L., Brambilla, E., Rovere-Querini, P., Capobianco, A., Alfaro-Cervello, C., Salani, G., Cossetti, C., Borsellino, G., Battistini, L., et al. Immune regulatory neural stem/precursor cells protect from central nervous system autoimmunity by restraining dendritic cell function. PLoS ONE 2009, 4, e5959.
212. Pluchino, S., Zanotti, L., Deleidi, M., Martino, G. Neural stem cells and their use as therapeutic tool in neurological disorders. Brain Res. Brain Res. Rev. 2005, 48, 211-219.
213. Einstein, O., Fainstein, N., Vaknin, I., Mizrachi-Kol, R., Reihartz, E., Grigoriadis, N., Lavon, I., Baniyash, M., Lassmann, H., Ben-Hur, T. Neural precursors attenuate autoimmune encephalomyelitis by peripheral immunosuppression. Ann. Neurol. 2007, 61, 209-218.
214. Einstein, O., Karussis, D., Grigoriadis, N., Mizrachi-Kol, R., Reinhartz, E., Abramsky, O., Ben-Hur, T. Intraventricular transplantation of neural precursor cell spheres attenuates acute experimental allergic encephalomyelitis. Mol. Cell. Neurosci. 2003, 24, 1074-1082.
215. Cusimano, M., Biziato, D., Brambilla, E., Donega, M., Alfaro-Cervello, C., Snider, S., Salani, G., Pucci, F., Comi, G., Garcia-Verdugo, J.M., et al. Transplanted neural stem/precursor cells instruct phagocytes and reduce secondary tissue damage in the injured spinal cord. Brain: J. Neurol. 2012, 135, 447-460.
216. Goodenough, D.A., Goliger, J.A., Paul, D.L. Connexins, connexons, and intercellular communication. Annu. Rev. Biochem. 1996, 65, 475-502.
217. Lakhal, S., Wood, M.J. Exosome nanotechnology: An emerging paradigm shift in drug delivery: exploitation of exosome nanovesicles for systemic in vivo delivery of RNAi heralds new horizons for drug delivery across biological barriers. Bioessays 2011, 33, 737-741.
218. Zhuang, X., Xiang, X., Grizzle, W., Sun, D., Zhang, S., Axtell, R.C., Ju, S., Mu, J., Zhang, L., Steinman, L., 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.
219. Clayton, A., Harris, C.L., Court, J., Mason, M.D., Morgan, B.P. Antigen-presenting cell exosomes are protected from complement-mediated lysis by expression of CD55 and CD59. Eur. J. Immunol. 2003, 33, 522-531.
220. Kooijmans, S.A., Vader, P., van Dommelen, S.M., van Solinge, W.W., Schiffelers, R.M. Exosome mimetics: A novel class of drug delivery systems. Int. J. Nanomed. 2012, 7, 1525-1541.
221. Chaput, N., Flament, C., Viaud, S., Taieb, J., Roux, S., Spatz, A., Andre, F., LePecq, J.B., Boussac, M., Garin, J., et al. Dendritic cell derived-exosomes: Biology and clinical implementations. J. Leukoc. Biol. 2006, 80, 471-478.
222. Wolfers, J., Lozier, A., Raposo, G., Regnault, A., Thery, C., Masurier, C., Flament, C., Pouzieux, S., Faure, F., Tursz, T., et al. Tumor-derived exosomes are a source of shared tumor rejection antigens for CTL cross-priming. Nat. Med. 2001, 7, 297-303.
223. Escudier, B., Dorval, T., Chaput, N., Andre, F., Caby, M.P., Novault, S., Flament, C., Leboulaire, C., Borg, C., Amigorena, S., et al. Vaccination of metastatic melanoma patients with autologous dendritic cell (DC) derived-exosomes: Results of thefirst phase I clinical trial. J. Transl. Med. 2005, 3, doi:10.1186/1479-5876-3-10.
224. Morse, M.A., Garst, J., Osada, T., Khan, S., Hobeika, A., Clay, T.M., Valente, N., Shreeniwas, R., Sutton, M.A., Delcayre, A., et al. A phase I study of dexosome immunotherapy in patients with advanced non-small cell lung cancer. J. Transl. Med. 2005, 3, doi:10.1186/1479-5876-3-9.
225. Peche, H., Renaudin, K., Beriou, G., Merieau, E., Amigorena, S., Cuturi, M.C. Induction of tolerance by exosomes and short-term immunosuppression in a fully MHC-mismatched rat cardiac allograft model. Am. J. Transpl. 2006, 6, 1541-1550.
226. Kim, S.H., Bianco, N.R., Shufesky, W.J., Morelli, A.E., Robbins, P.D. MHC class II+ exosomes in plasma suppress inflammation in an antigen-specific and Fas ligand/Fas-dependent manner. J. Immunol. 2007, 179, 2235-2241.
227. Drago, D., Cossetti, C., Iraci, N., Gaude, E., Musco, G., Bachi, A., Pluchino, S. The stem cell secretome and its role in brain repair. Biochimie 2013, 95, 2271-2285.
228. De Jong, O.G., van Balkom, B.W., Schiffelers, R.M., Bouten, C.V., Verhaar, M.C. Extracellular vesicles: Potential roles in regenerative medicine. Front. Immunol. 2014, 5, 608, doi:10.3389/fimmu.2014.00608.
229. Zhang, B., Yin, Y., Lai, R.C., Tan, S.S., Choo, A.B., Lim, S.K. Mesenchymal stem cells secrete immunologically active exosomes. Stem Cells Dev. 2014, 23, 1233-1244.
230. Lee, J.K., Park, S.R., Jung, B.K., Jeon, Y.K., Lee, Y.S., Kim, M.K., Kim, Y.G., Jang, J.Y., Kim, C.W. Exosomes derived from mesenchymal stem cells suppress angiogenesis by down-regulating VEGF expression in breast cancer cells. PLoS ONE 2013, 8, e84256, doi:10.1371/journal.pone.0084256.
231. Soki, F.N., Koh, A.J., Jones, J.D., Kim, Y.W., Dai, J., Keller, E.T., Pienta, K.J., Atabai, K., Roca, H., McCauley, L.K. Polarization of prostate cancer-associated macrophages is induced by milk fat globule-EGF factor 8 (MFG-E8)-mediated efferocytosis. J. Biol. Chem. 2014, 289, 24560-24572.
232. Mokarizadeh, A., Delirezh, N., Morshedi, A., Mosayebi, G., Farshid, A.A., Mardani, K. Microvesicles derived from mesenchymal stem cells: Potent organelles for induction of tolerogenic signaling. Immunol. Lett. 2012, 147, 47-54.
233. Arslan, F., Lai, R.C., Smeets, M.B., Akeroyd, L., Choo, A., Aguor, E.N., Timmers, L., van Rijen, H.V., Doevendans, P.A., Pasterkamp, G., et al. 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 Cells Res. 2013, 10, 301-312.
234. Zou, X., Zhang, G., Cheng, Z., Yin, D., Du, T., Ju, G., Miao, S., Liu, G., Lu, M., Zhu, Y. Microvesicles derived from human Wharton’s Jelly mesenchymal stromal cells ameliorate renal ischemia-reperfusion injury in rats by suppressing CX3CL1. Stem Cell Res. Ther. 2014, 5, 40, doi:10.1186/scrt428.
235. Xin, H., Li, Y., Buller, B., Katakowski, M., Zhang, Y., Wang, X., Shang, X., Zhang, Z.G., Chopp, M. Exosome-mediated transfer of miR-133b from multipotent mesenchymal stromal cells to neural cells contributes to neurite outgrowth. Stem Cells 2012, 30, 1556-1564.
236. Waldenstrom, A., Genneback, N., Hellman, U., Ronquist, G. Cardiomyocyte microvesicles contain DNA/RNA and convey biological messages to target cells. PLoS ONE 2012, 7, e34653, doi:10.1371/journal.pone.0034653.
237. Yeo, R.W., Lai, R.C., Zhang, B., Tan, S.S., Yin, Y., Teh, B.J., Lim, S.K. Mesenchymal stem cell: An efficient mass producer of exosomes for drug delivery. Adv. Drug Deliv. Rev. 2013, 65, 336-341.
238. Chen, J., Li, Y., Wang, L., Zhang, Z., Lu, D., Lu, M., Chopp, M. Therapeutic benefit of intravenous administration of bone marrow stromal cells after cerebral ischemia in rats. Stroke 2001, 32, 1005-1011.
239. Shen, L.H., Li, Y., Chen, J., Zhang, J., Vanguri, P., Borneman, J., Chopp, M. Intracarotid transplantation of bone marrow stromal cells increases axon-myelin remodeling after stroke. Neuroscience 2006, 137, 393-399.
240. Chopp, M., Li, Y. Treatment of neural injury with marrow stromal cells. Lancet Neurol. 2002, 1, 92-100.
241. Chu, K., Kim, M., Jeong, S.W., Kim, S.U., Yoon, B.W. Human neural stem cells can migrate, differentiate, and integrate after intravenous transplantation in adult rats with transient forebrain ischemia. Neurosci. Lett. 2003, 343, 129-133.
242. Chu, K., Kim, M., Park, K.I., Jeong, S.W., Park, H.K., Jung, K.H., Lee, S.T., Kang, L., Lee, K., Park, D.K., et al. Human neural stem cells improve sensorimotor deficits in the adult rat brain with experimental focal ischemia. Brain Res. 2004, 1016, 145-153.
243. Jakel, R.J., Schneider, B.L., Svendsen, C.N. Using human neural stem cells to model neurological disease. Nat. Rev. Genet. 2004, 5, 136-144.
244. Miller, R.H., Bai, L. Translating stem cell therapies to the clinic. Neurosci. Lett. 2012, 519, 87-92.
245. Lai, R.C., Arslan, F., Lee, M.M., Sze, N.S., Choo, A., Chen, T.S., Salto-Tellez, M., Timmers, L., Lee, C.N., El Oakley, R.M., et al. Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury. Stem Cell Res. 2010, 4, 214-222.
246. Jeyaseelan, K., Lim, K.Y., Armugam, A. MicroRNA expression in the blood and brain of rats subjected to transient focal ischemia by middle cerebral artery occlusion. Stroke 2008, 39, 959-966.
247. Liu, F.J., Lim, K.Y., Kaur, P., Sepramaniam, S., Armugam, A., Wong, P.T., Jeyaseelan, K. MicroRNAs Involved in Regulating Spontaneous Recovery in Embolic Stroke Model. PLoS ONE 2013, 8, e66393.
248. Lusardi, T.A., Murphy, S.J., Phillips, J.I., Chen, Y., Davis, C.M., Young, J.M., Thompson, S.J., Saugstad, J.A. MicroRNA responses to focal cerebral ischemia in male and female mouse brain. Front. Mol. Neurosci. 2014, 7, doi:10.3389/fnmol.2014.00011.
249. Li, Y., Chen, J., Wang, L., Lu, M., Chopp, M. Treatment of stroke in rat with intracarotid administration of marrow stromal cells. Neurology 2001, 56, 1666-1672.
250. Koh, W., Sheng, C.T., Tan, B., Lee, Q.Y., Kuznetsov, V., Kiang, L.S., Tanavde, V. Analysis of deep sequencing microRNA expression profile from human embryonic stem cells derived mesenchymal stem cells reveals possible role of let-7 microRNA family in downstream targeting of hepatic nuclear factor 4α. BMC Genom. 2010, 11, S6, doi:10.1186/1471-2164-11-S1-S6.
251. Xin, H., Li, Y., Shen, L.H., Liu, X., Hozeska-Solgot, A., Zhang, R.L., Zhang, Z.G., Chopp, M. Multipotent mesenchymal stromal cells increase tPA expression and concomitantly decrease PAI-1 expression in astrocytes through the sonic hedgehog signaling pathway after stroke (in vitro study). J. Cereb. Blood Flow Metab. 2011, 31, 2181-2188.
252. Ono, M., Kosaka, N., Tominaga, N., Yoshioka, Y., Takeshita, F., Takahashi, R.U., Yoshida, M., Tsuda, H., Tamura, K., Ochiya, T. Exosomes from bone marrow mesenchymal stem cells contain a microRNA that promotes dormancy in metastatic breast cancer cells. Sci. Signal. 2014, 7, ra63, doi:10.1126/scisignal.2005231.
253. Xin, H., Li, Y., Chopp, M. Exosomes/miRNAs as mediating cell-based therapy of stroke. Front. Cell. Neurosci. 2014, 8, doi:10.3389/fncel.2014.00377.
254. Xin, H., Li, Y., Shen, L.H., Liu, X., Wang, X., Zhang, J., Pourabdollah-Nejad, D.S., Zhang, C., Zhang, L., Jiang, H., et al. Increasing tPA activity in astrocytes induced by multipotent mesenchymal stromal cells facilitate neurite outgrowth after stroke in the mouse. PLoS ONE 2010, 5, e9027.
255. Yu, Y.M., Gibbs, K.M., Davila, J., Campbell, N., Sung, S., Todorova, T.I., Otsuka, S., Sabaawy, H.E., Hart, R.P., Schachner, M. MicroRNA miR-133b is essential for functional recovery after spinal cord injury in adult zebrafish. Eur. J. Neurosci. 2011, 33, 1587-1597.
256. Pusic, A.D., Pusic, K.M., Clayton, B.L., Kraig, R.P. IFNγ-stimulated dendritic cell exosomes as a potential therapeutic for remyelination. J. Neuroimmunol. 2014, 266, 12-23.
257. Pusic, A.D., Pusic, K.M., Kraig, R.P. What are exosomes and how can they be used in multiple sclerosis therapy? Expert Rev. Neurother. 2014, 14, 353-355.
258. Kalani, A., Tyagi, A., Tyagi, N. Exosomes: Mediators of neurodegeneration, neuroprotection and therapeutics. Mol. Neurobiol. 2014, 49, 590-600.
259. Putz, U., Howitt, J., Lackovic, J., Foot, N., Kumar, S., Silke, J., Tan, S.S. Nedd4 family-interacting protein 1 (Ndfip1) is required for the exosomal secretion of Nedd4 family proteins. J. Biol. Chem. 2008, 283, 32621-32627.
260. Ferrari, D., Chiozzi, P., Falzoni, S., Dal Susino, M., Collo, G., Buell, G., di Virgilio, F. ATP-mediated cytotoxicity in microglial cells. Neuropharmacology 1997, 36, 1295-1301.
261. Lamichhane, T.N., Sokic, S., Schardt, J.S., Raiker, R.S., Lin, J.W., Jay, S.M. Emerging roles for extracellular vesicles in tissue engineering and regenerative medicine. Tissue Eng. Part B Rev. 2015, 21, 45-54.
262. Zhang, H.C., Liu, X.B., Huang, S., Bi, X.Y., Wang, H.X., Xie, L.X., Wang, Y.Q., Cao, X.F., Lv, J., Xiao, F.J., et al. Microvesicles derived from human umbilical cord mesenchymal stem cells stimulated by hypoxia promote angiogenesis both in vitro and in vivo. Stem Cells Dev. 2012, 21, 3289-3297.
263. Bian, S., Zhang, L., Duan, L., Wang, X., Min, Y., Yu, H. Extracellular vesicles derived from human bone marrow mesenchymal stem cells promote angiogenesis in a rat myocardial infarction model. J. Mol. Med. 2014, 92, 387-397.
264. Lopatina, T., Bruno, S., Tetta, C., Kalinina, N., Porta, M., Camussi, G. Platelet-derived growth factor regulates the secretion of extracellular vesicles by adipose mesenchymal stem cells and enhances their angiogenic potential. Cell Commun. Signal. 2014, 12, doi:10.1186/1478-811X-12-26.
265. Alvarez-Erviti, L., Seow, Y., Yin, H., Betts, C., Lakhal, S., Wood, M.J. Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat. Biotechnol. 2011, 29, 341-345.
266. Olson, S.D., Kambal, A., Pollock, K., Mitchell, G.M., Stewart, H., Kalomoiris, S., Cary, W., Nacey, C., Pepper, K., Nolta, J.A. Examination of mesenchymal stem cell-mediated RNAi transfer to Huntington’s disease affected neuronal cells for reduction of huntingtin. Mol. Cell. Neurosci. 2012, 49, 271-281.
267. Olson, S.D., Pollock, K., Kambal, A., Cary, W., Mitchell, G.M., Tempkin, J., Stewart, H., McGee, J., Bauer, G., Kim, H.S., et al. Genetically engineered mesenchymal stem cells as a proposed therapeutic for Huntington’s disease. Mol. Neurobiol. 2012, 45, 87-98.
268. Ohno, S., Takanashi, M., Sudo, K., Ueda, S., Ishikawa, A., Matsuyama, N., Fujita, K., Mizutani, T., Ohgi, T., Ochiya, T., et al. Systemically injected exosomes targeted to EGFR deliver antitumor microRNA to breast cancer cells. Mol. Ther. 2013, 21, 185-191.
269. Katakowski, M., Buller, B., Zheng, X., Lu, Y., Rogers, T., Osobamiro, O., Shu, W., Jiang, F., Chopp, M. Exosomes from marrow stromal cells expressing miR-146b inhibit glioma growth. Cancer Lett. 2013, 335, 201-204.
270. Fang, Y., Wu, N., Gan, X., Yan, W., Morrell, J.C., Gould, S.J. Higher-order oligomerization targets plasma membrane proteins and HIV gag to exosomes. PLoS Biol. 2007, 5, e158, doi:10.1371/journal.pbio.0050158.
271. Yang, J.M., Gould, S.J. The cis-acting signals that target proteins to exosomes and microvesicles. Biochem. Soc. Trans. 2013, 41, 277-282.
272. Sun, D., Zhuang, X., Xiang, X., Liu, Y., Zhang, S., Liu, C., Barnes, S., Grizzle, W., Miller, D., Zhang, H.G. A novel nanoparticle drug delivery system: The anti-inflammatory activity of curcumin is enhanced when encapsulated in exosomes. Mol. Ther. 2010, 18, 1606-1614.
273. Ohno, S.I., Drummen, G.P.C., Kuroda, M. Focus on extracellular vesicles: Development of exosome-based therapeutic systems. Int. J. Mol. Sci. 2016, 17, doi:10.3390/ijms17020172.
274. Vella, L.J., Hill, A.F., Cheng, L. Focus on extracellular vesicles: Exosomes and their role in protein trafficking in alzheimer’s and parkinson's disease. Int. J. Mol. Sci. 2016, 17, doi:10.3390/ijms17020173.
275. Zhang, B., Tan, K.H., Lim, S.K. Focus on extracellular vesicles: Therapeutic efficacy of stem cell-derived extracellular vesicles. Int. J. Mol. Sci. 2016, 17, doi:10.3390/ijms17020174.