Re-Engineering Extracellular Vesicles as Smart Nanoscale Therapeutics

ACS Nano

Volumn 11, Issue 1, 2017, Pages 69-83

  Armstrong, James P K ^a   Holme, Margaret N ^a   Stevens, Molly M ^a  

^a IMPERIAL COLLEGE LONDON   (United Kingdom)

Author keywords

cell free therapy; drug loading; exosomes; extracellular vesicles; functionalization; genetic manipulation; membrane modification; microvesicles

Indexed keywords

BIOCOMPATIBILITY; CELL MEMBRANES; CYTOLOGY; DISEASES; METABOLIC ENGINEERING; MOLECULAR BIOLOGY; REENGINEERING; RNA; SIGNAL TRANSDUCTION; SURFACE CHEMISTRY;

CELL-FREE; DRUG LOADING; EXOSOMES; EXTRACELLULAR; FUNCTIONALIZATIONS; GENETIC MANIPULATIONS; MEMBRANE MODIFICATION; MICROVESICLES;

CELL ENGINEERING;

DRUG; NANOPARTICLE; PEPTIDE; RNA;

ANIMAL; CHEMICAL PHENOMENA; CHEMISTRY; DRUG DELIVERY SYSTEM; EXOSOME; HUMAN; METABOLISM; NANOMEDICINE; PROCEDURES;

ANIMALS; DRUG DELIVERY SYSTEMS; EXTRACELLULAR VESICLES; HUMANS; HYDROPHOBIC AND HYDROPHILIC INTERACTIONS; NANOMEDICINE; NANOPARTICLES; PEPTIDES; PHARMACEUTICAL PREPARATIONS; RNA;

EID: 85018192726     PISSN: 19360851     EISSN: 1936086X     Source Type: Journal    
DOI: 10.1021/acsnano.6b07607     Document Type: Review

References (183)

1. Raposo, G.; Stoorvogel, W. Extracellular Vesicles: Exosomes, Microvesicles, and Friends J. Cell Biol. 2013, 200, 373-383 10.1083/jcb.201211138
2. Gould, S. J.; Raposo, G. As We Wait: Coping with an Imperfect Nomenclature for Extracellular Vesicles J. Extracell. Vesicles 2013, 2, 3-5 10.3402/jev.v2i0.20389
3. Théry, C.; Zitvogel, L.; Amigorena, S. Exosomes: Composition, Biogenesis and Function Nat. Rev. Immunol. 2002, 2, 569-579
4. Gyorgy, B.; Szabo, R. G.; Pasztoi, M.; Pal, Z.; Misjak, P.; Aradi, B.; Laszlo, V.; Pallinger, E.; Pap, E.; Kittel, A.; Nagy, G.; Falus, A.; Buzas, E. I. Membrane Vesicles, Current State-of-the-Art: Emerging Role of Extracellular Vesicles Cell. Mol. Life Sci. 2011, 68, 2667-2688 10.1007/s00018-011-0689-3
5. El Andaloussi, S.; Mäger, I.; Breakefield, X. O.; Wood, M. J. A. Extracellular Vesicles: Biology and Emerging Therapeutic Opportunities Nat. Rev. Drug Discovery 2013, 12, 347-357 10.1038/nrd3978
6. Raposo, G. B Lymphocytes Secrete Antigen-presenting Vesicles J. Exp. Med. 1996, 183, 1161-1172
7. Rosenthal, A. K.; Gohr, C. M.; Ninomiya, J.; Wakim, B. T. Proteomic Analysis of Articular Cartilage Vesicles from Normal and Osteoarthritic Cartilage Arthritis Rheum. 2011, 63, 401-411 10.1002/art.30120
8. Sarkar, A.; Mitra, S.; Mehta, S.; Raices, R.; Wewers, M. D. Monocyte Derived Microvesicles Deliver a Cell Death Message via Encapsulated Caspase-1 PLoS One 2009, 4, e7140 10.1371/journal.pone.0007140
9. Esser, J.; Gehrmann, U.; D'Alexandri, F. L.; Hidalgo-Estevez, A. M.; Wheelock, C. E.; Scheynius, A.; Gabrielsson, S.; Radmark, O. Exosomes from Human Macrophages and Dendritic Cells Contain Enzymes for Leukotriene Biosynthesis and Promote Granulocyte Migration J. Allergy Clin. Immunol. 2010, 126, 1032-1040 10.1016/j.jaci.2010.06.039
10. Guescini, M.; Genedani, S.; Stocchi, V.; Agnati, L. F. Astrocytes and Glioblastoma Cells Release Exosomes Carrying mtDNA J. Neural Transm. 2010, 117, 1-4 10.1007/s00702-009-0288-8
11. Guescini, M.; Guidolin, D.; Vallorani, L.; Casadei, L.; Gioacchini, A. M.; Tibollo, P.; Battistelli, M.; Falcieri, E.; Battistin, L.; Agnati, L. F.; Stocchi, V. C2C12 Myoblasts Release Micro-Vesicles Containing mtDNA and Proteins Involved in Signal Transduction Exp. Cell Res. 2010, 316, 1977-1984 10.1016/j.yexcr.2010.04.006
12. Valadi, H.; Ekström, K.; Bossios, A.; Sjöstrand, M.; Lee, J. J.; Lötvall, 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 10.1038/ncb1596
13. Skog, J.; Würdinger, T.; van Rijn, S.; Meijer, D. H.; Gainche, L.; Sena-Esteves, M.; Curry, W. T.; 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 10.1038/ncb1800
14. Hunter, M. P.; Ismail, N.; Zhang, X.; Aguda, B. D.; Lee, E. J.; Yu, L.; Xiao, T.; Schafer, J.; Lee, M. L. T.; Schmittgen, T. D.; Nan-Sinkam, S. P.; Jarjoura, D.; Marsh, C. B. Detection of microRNA Expression in Human Peripheral Blood Microvesicles PLoS One 2008, 3, e3694 10.1371/journal.pone.0003694
15. Taylor, D. D.; Gercel-Taylor, C. MicroRNA Signatures of Tumor-Derived Exosomes as Diagnostic Biomarkers of Ovarian Cancer Gynecol. Oncol. 2008, 110, 13-21 10.1016/j.ygyno.2008.04.033
16. Ferguson, S. W.; Nguyen, J. Exosomes as Therapeutics: The Implications of Molecular Composition and Exosomal Heterogeneity J. Controlled Release 2016, 228, 179-190 10.1016/j.jconrel.2016.02.037
17. Caby, M.-P.; Lankar, D.; Vincendeau-Scherrer, C.; Raposo, G.; Bonnerot, C. Exosomal-like Vesicles Are Present in Human Blood Plasma Int. Immunol. 2005, 17, 879-887 10.1093/intimm/dxh267
18. Admyre, C.; Johansson, S. M.; Qazi, K. R.; Filén, J.-J.; Lahesmaa, R.; Norman, M.; Neve, E. P. A.; Scheynius, A.; Gabrielsson, S. Exosomes with Immune Modulatory Features Are Present in Human Breast Milk J. Immunol. 2007, 179, 1969-1978 10.4049/jimmunol.179.3.1969
19. Pisitkun, T.; Shen, R.-F.; Knepper, M. A. Identification and Proteomic Profiling of Exosomes in Human Urine Proc. Natl. Acad. Sci. U. S. A. 2004, 101, 13368-13373 10.1073/pnas.0403453101
20. Ogawa, Y.; Miura, Y.; Harazono, A.; Kanai-Azuma, M.; Akimoto, Y.; Kawakami, H.; Yamaguchi, T.; Toda, T.; Endo, T.; Tsubuki, M.; Yanoshita, R. Proteomic Analysis of Two Types of Exosomes in Human Whole Saliva Biol. Pharm. Bull. 2011, 34, 13-23 10.1248/bpb.34.13
21. Skriner, K.; Adolph, K.; Jungblut, P. R.; Burmester, G. R. Association of Citrullinated Proteins with Synovial Exosomes Arthritis Rheum. 2006, 54, 3809-3814 10.1002/art.22276
22. Masyuk, A. I.; Huang, B. Q.; Ward, C. J.; Gradilone, S. A.; Banales, J. M.; Masyuk, T. V.; Radtke, B.; Splinter, P. L.; LaRusso, N. F. Biliary Exosomes Influence Cholangiocyte Regulatory Mechanisms and Proliferation through Interaction with Primary Cilia Am. J. Physiol. Gastrointest. Liver Physiol. 2010, 299, G990-G999 10.1152/ajpgi.00093.2010
23. Asea, A.; Jean-Pierre, C.; Kaur, P.; Rao, P.; Linhares, I. M.; Skupski, D.; Witkin, S. S. Heat Shock Protein-Containing Exosomes in Mid-Trimester Amniotic Fluids J. Reprod. Immunol. 2008, 79, 12-17 10.1016/j.jri.2008.06.001
24. Ronquist, G.; Brody, I. The Prostasome: Its Secretion and Function in Man Biochim. Biophys. Acta, Rev. Biomembr. 1985, 822, 203-218 10.1016/0304-4157(85)90008-5
25. Andre, F.; Schartz, N. E. C.; Movassagh, M.; Flament, C.; Pautier, P.; Morice, P.; Pomel, C.; Lhomme, C.; Escudier, B.; Le Chevalier, T.; Tursz, T.; Amigorena, S.; Raposo, G.; Angevin, E.; Zitvogel, L. Malignant Effusions and Immunogenic Tumour-Derived Exosomes Lancet 2002, 360, 295-305 10.1016/S0140-6736(02)09552-1
26. Shedden, K.; Xie, X. T.; Chandaroy, P.; Chang, Y. T.; Rosania, G. R. Expulsion of Small Molecules in Vesicles Shed by Cancer Cells: Association with Gene Expression and Chemosensitivity Profiles Cancer Res. 2003, 63, 4331-4337
27. Yáñez-Mó, M.; Siljander, P. R.-M.; Andreu, Z.; Zavec, A. B.; Borràs, F. E.; Buzas, E. I.; Buzas, K.; Casal, E.; Cappello, F.; Carvalho, J.; Colas, E.; Cordeiro-da Silva, A.; Fais, S.; Falcon-Perez, J. M.; Ghobrial, I. M.; Giebel, B.; Gimona, M.; Graner, M.; Gursel, I.; Gursel, M. et al. Biological Properties of Extracellular Vesicles and Their Physiological Functions J. Extracell. Vesicles 2015, 4, 27066 10.3402/jev.v4.27066
28. Mulcahy, L. A.; Pink, R. C.; Carter, D. R. F. Routes and Mechanisms of Extracellular Vesicle Uptake J. Extracell. Vesicles 2014, 3, 24641 10.3402/jev.v3.24641
29. Montecalvo, A.; Shufesky, W. J.; Stolz, D. B.; Sullivan, M. G.; Wang, Z.; Divito, S. J.; Papworth, G. D.; Watkins, S. C.; Robbins, P. D.; Larregina, A. T.; Morelli, A. E. Exosomes as a Short-Range Mechanism to Spread Alloantigen between Dendritic Cells during T Cell Allorecognition J. Immunol. 2008, 180, 3081-3090 10.4049/jimmunol.180.5.3081
30. Morelli, A. E.; Larregina, A. T.; Shufesky, W. J.; Sullivan, M. L. G.; Stolz, D. B.; Papworth, G. D.; Zahorchak, A. F.; Logar, A. J.; Wang, Z.; Watkins, S. C.; Falo, L. D.; Thomson, A. W. Endocytosis, Intracellular Sorting, and Processing of Exosomes by Dendritic Cells Blood 2004, 104, 3257-3266 10.1182/blood-2004-03-0824
31. 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 10.1242/jcs.074088
32. Feng, D.; Zhao, W. L.; Ye, Y. Y.; Bai, X. C.; Liu, R. Q.; Chang, L. F.; Zhou, Q.; Sui, S. F. Cellular Internalization of Exosomes Occurs through Phagocytosis Traffic 2010, 11, 675-687 10.1111/j.1600-0854.2010.01041.x
33. Montecalvo, A.; Larregina, A. T.; Shufesky, W. J.; Stolz, D. B.; Sullivan, M. L. G.; Karlsson, J. M.; Baty, C. J.; Gibson, G. A.; Erdos, G.; Wang, Z.; Milosevic, J.; Tkacheva, O. A.; Divito, S. J.; Jordan, R.; Lyons-Weiler, J.; Watkins, S. C.; Morelli, A. E. Mechanism of Transfer of Functional microRNAs between Mouse Dendritic Cells via Exosomes Blood 2012, 119, 756-766 10.1182/blood-2011-02-338004
34. Al-Nedawi, K.; Meehan, B.; Kerbel, R. S.; Allison, A. C.; Rak, J. Endothelial Expression of Autocrine VEGF upon the Uptake of Tumor-Derived Microvesicles Containing Oncogenic EGFR Proc. Natl. Acad. Sci. U. S. A. 2009, 106, 3794-3799 10.1073/pnas.0804543106
35. Baj-Krzyworzeka, M.; Majka, M.; Pratico, D.; Ratajczak, J.; Vilaire, G.; Kijowski, J.; Reca, R.; Janowska-Wieczorek, A.; Ratajczak, M. Z. Platelet-Derived Microparticles Stimulate Proliferation, Survival, Adhesion, and Chemotaxis of Hematopoietic Cells Exp. Hematol. 2002, 30, 450-459 10.1016/S0301-472X(02)00791-9
36. Baj-Krzyworzeka, M.; Szatanek, R.; Weglarczyk, K.; Baran, J.; Urbanowicz, B.; Brański, P.; Ratajczak, M. Z.; Zembala, M. Tumour-Derived Microvesicles Carry Several Surface Determinants and mRNA of Tumour Cells and Transfer Some of These Determinants to Monocytes Cancer Immunol. Immunother. 2006, 55, 808-818 10.1007/s00262-005-0075-9
37. 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 10.1038/sj.leu.2404132
38. Rozmyslowicz, T.; Majka, M.; Kijowski, J.; Murphy, S. L.; Conover, D. O.; Poncz, M.; Ratajczak, J.; Gaulton, G. N.; Ratajczak, M. Z. Platelet- and Megakaryocyte-Derived Microparticles Transfer CXCR4 Receptor to CXCR4-Null Cells and Make Them Susceptible to Infection by X4-HIV AIDS 2003, 17, 33-42 10.1097/00002030-200301030-00006
39. Ratajczak, J.; Wysoczynski, M.; Hayek, F.; Janowska-Wieczorek, A.; Ratajczak, M. Z. Membrane-Derived Microvesicles: Important and Underappreciated Mediators of Cell-to-Cell Communication Leukemia 2006, 20, 1487-1495 10.1038/sj.leu.2404296
40. Anderson, H. C.; Mulhall, D.; Garimella, R. Role of Extracellular Membrane Vesicles in the Pathogenesis of Various Diseases, Including Cancer, Renal Diseases, Atherosclerosis, and Arthritis Lab. Invest. 2010, 90, 1549-1557 10.1038/labinvest.2010.152
41. Buzas, E. I.; Gyorgy, B.; Nagy, G.; Falus, A.; György, B.; Nagy, G.; Falus, A.; Gay, S. Emerging Role of Extracellular Vesicles in Inflammatory Diseases Nat. Rev. Rheumatol. 2014, 10, 356-364 10.1038/nrrheum.2014.19
42. Aharon, A.; Brenner, B. Microparticles, Thrombosis and Cancer Best Pract. Res. Clin. Haematol. 2009, 22, 61-69 10.1016/j.beha.2008.11.002
43. Fuhrmann, G.; Herrmann, I. K.; Stevens, M. M. Cell-Derived Vesicles for Drug Therapy and Diagnostics: Opportunities and Challenges Nano Today 2015, 10, 397-409 10.1016/j.nantod.2015.04.004
44. Gnecchi, M.; He, H.; Liang, O. D.; Melo, L. G.; Morello, F.; Mu, H.; Noiseux, N.; Zhang, L.; Pratt, R. E.; Ingwall, J. S.; Dzau, V. J. Paracrine Action Accounts for Marked Protection of Ischemic Heart by Akt-Modified Mesenchymal Stem Cells Nat. Med. 2005, 11, 367-368 10.1038/nm0405-367
45. Yang, L.; Wu, X.-H.; Wang, D.; Luo, C.-L.; Chen, L.-X. Bladder Cancer Cell-Derived Exosomes Inhibit Tumor Cell Apoptosis and Induce Cell Proliferation in Vitro Mol. Med. Rep. 2013, 8, 1272-1278 10.3892/mmr.2013.1634
46. Inder, K. L.; Ruelcke, J. E.; Petelin, L.; Moon, H.; Choi, E.; Rae, J.; Blumenthal, A.; Hutmacher, D.; Saunders, N. A.; Stow, J. L.; Parton, R. G.; Hill, M. M. Cavin-1/PTRF Alters Prostate Cancer Cell-Derived Extracellular Vesicle Content and Internalization to Attenuate Extracellular Vesicle-Mediated Osteoclastogenesis and Osteoblast Proliferation J. Extracell. Vesicles 2014, 3, 23784 10.3402/jev.v3.23784
47. Deregibus, M. C.; Cantaluppi, V.; Calogero, R.; Iacono, M.; Lo; 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 10.1182/blood-2007-03-078709
48. Janowska-Wieczorek, A.; Wysoczynski, M.; Kijowski, J.; Marquez-Curtis, L.; Machalinski, B.; Ratajczak, J.; Ratajczak, M. Z. Microvesicles Derived from Activated Platelets Induce Metastasis and Angiogenesis in Lung Cancer Int. J. Cancer 2005, 113, 752-760 10.1002/ijc.20657
49. 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.; Yang, Y.; Guo, Z.-K. 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 10.1089/scd.2012.0095
50. van Balkom, B. W. M.; De Jong, O. G.; Smits, M.; Brummelman, J.; Den Ouden, K.; De Bree, P. M.; Van Eijndhoven, M. A. J.; Pegtel, D. M.; Stoorvogel, W.; Wurdinger, T.; Verhaar, M. C. Endothelial Cells Require miR-214 to Secrete Exosomes That Suppress Senescence and Induce Angiogenes in Human and Mouse Endothelial Cells Blood 2013, 121, 3997-4006 10.1182/blood-2013-02-478925
51. Hong, B. S.; Cho, J.-H.; Kim, H.; Choi, E.-J.; Rho, S.; Kim, J.; Kim, J. H.; Choi, D.-S.; Kim, Y.-K.; Hwang, D.; Gho, Y. S. Colorectal Cancer Cell-Derived Microvesicles Are Enriched in Cell Cycle-Related mRNAs That Promote Proliferation of Endothelial Cells BMC Genomics 2009, 10, 556 10.1186/1471-2164-10-556
52. Kucharzewska, P.; Christianson, H. C.; Welch, J. E.; Svensson, K. J.; Fredlund, E.; Ringnér, M.; Mörgelin, M.; Bourseau-Guilmain, E.; Bengzon, J.; Belting, M. Exosomes Reflect the Hypoxic Status of Glioma Cells and Mediate Hypoxia-Dependent Activation of Vascular Cells during Tumor Development Proc. Natl. Acad. Sci. U. S. A. 2013, 110, 7312-7317 10.1073/pnas.1220998110
53. 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. Signaling 2014, 12, 26 10.1186/1478-811X-12-26
54. Sheldon, H.; Heikamp, E.; Turley, H.; Dragovic, R.; Thomas, P.; Oon, C. E.; Leek, R.; Edelmann, M.; Kessler, B.; Sainson, R. C. A.; Sargent, I.; Li, J.-L.; Harris, A. L. New Mechanism for Notch Signaling to Endothelium at a Distance by Delta-like 4 Incorporation into Exosomes Blood 2010, 116, 2385-2394 10.1182/blood-2009-08-239228
55. Sahoo, S.; Klychko, E.; Thorne, T.; Misener, S.; Schultz, K. M.; Millay, M.; Ito, A.; Liu, T.; Kamide, C.; Agrawal, H.; Perlman, H.; Qin, G.; Kishore, R.; Losordo, D. W. Exosomes from Human CD34+ Stem Cells Mediate Their Proangiogenic Paracrine Activity Circ. Res. 2011, 109, 724-728 10.1161/CIRCRESAHA.111.253286
56. Théry, C.; Duban, L.; Segura, E.; Véron, P.; Lantz, O.; Amigorena, S. Indirect Activation of Naïve CD4+ T Cells by Dendritic Cell-Derived Exosomes Nat. Immunol. 2002, 3, 1156-1162 10.1038/ni854
57. Lu, C.-W.; Hung, Y.; Hsiao, J.-K.; Yao, M.; Chung, T.-H.; Lin, Y.-S.; Wu, S.-H.; Hsu, S.-C.; Liu, H.-M.; Mou, C.-Y.; Yang, C.-S.; Huang, D.-M.; Chen, Y.-C. Bifunctional Magnetic Silica Nanoparticles for Highly Efficient Human Stem Cell Labeling Nano Lett. 2007, 7, 149-154 10.1021/nl0624263
58. Bhatnagar, S.; Schorey, J. S. Exosomes Released from Infected Macrophages Contain Mycobacterium Avium Glycopeptidolipids and Are Proinflammatory J. Biol. Chem. 2007, 282, 25779-25789 10.1074/jbc.M702277200
59. Vega, V. L.; Rodríguez-Silva, M.; Frey, T.; Gehrmann, M.; Diaz, J. C.; Steinem, C.; Multhoff, G.; Arispe, N.; De Maio, A. Hsp70 Translocates into the Plasma Membrane after Stress and Is Released into the Extracellular Environment in a Membrane-Associated Form That Activates Macrophages J. Immunol. 2008, 180, 4299-4307 10.4049/jimmunol.180.6.4299
60. 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 10.1371/journal.pone.0011469
61. Alexander, M.; Hu, R.; Runtsch, M. C.; Kagele, D. A.; Mosbruger, T. L.; Tolmachova, T.; Seabra, M. C.; Round, J. L.; Ward, D. M.; O'Connell, R. M. Exosome-Delivered microRNAs Modulate the Inflammatory Response to Endotoxin Nat. Commun. 2015, 6, 7321 10.1038/ncomms8321
62. 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 10.1158/0008-5472.CAN-06-3456
63. Del Conde, I.; Shrimpton, C. N.; Thiagarajan, P.; Lopez, J. A. Tissue-Factor-Bearing Microvesicles Arise from Lipid Rafts and Fuse with Activated Platelets to Initiate Coagulation Blood 2005, 106, 1604-1612 10.1182/blood-2004-03-1095
64. Ekstrom, K.; Omar, O.; Graneli, C.; Wang, X.; Vazirisani, F.; Thomsen, P. Monocyte Exosomes Stimulate the Osteogenic Gene Expression of Mesenchymal Stem Cells PLoS One 2013, 8, e75227 10.1371/journal.pone.0075227
65. Nair, R.; Santos, L.; Awasthi, S.; von Erlach, T.; Chow, L. W.; Bertazzo, S.; Stevens, M. M. Extracellular Vesicles Derived from Preosteoblasts Influence Embryonic Stem Cell Differentiation Stem Cells Dev. 2014, 23, 1625-1635 10.1089/scd.2013.0633
66. Janowska-Wieczorek, A.; Majka, M.; Kijowski, J.; Baj-Krzyworzeka, M.; Reca, R.; Turner, A. R.; Ratajczak, J.; Emerson, S. G.; Kowalska, M. A.; Ratajczak, M. Z. Platelet-Derived Microparticles Bind to Hematopoietic Stem/progenitor Cells and Enhance Their Engraftment Blood 2001, 98, 3143-3149 10.1182/blood.V98.10.3143
67. Lai, R. C.; Arslan, F.; Lee, M. M.; Sze, N. S. K.; Choo, A.; Chen, T. S.; Salto-Tellez, M.; Timmers, L.; Lee, C. N.; El Oakley, R. M.; Pasterkamp, G.; De Kleijn, D. P. V.; Lim, S. K. Exosome Secreted by MSC Reduces Myocardial Ischemia/reperfusion Injury Stem Cell Res. 2010, 4, 214-222 10.1016/j.scr.2009.12.003
68. Arslan, F.; Lai, R. C.; Smeets, M. B.; Akeroyd, L.; Choo, A.; Aguor, E. N. E.; Timmers, L.; Van Rijen, H. V.; Doevendans, P. A.; Pasterkamp, G.; Lim, S. K.; De Kleijn, D. P. 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. 2013, 10, 301-312 10.1016/j.scr.2013.01.002
69. Barile, L.; Lionetti, V.; Cervio, E.; Matteucci, M.; Gherghiceanu, M.; Popescu, L. M.; Torre, T.; Siclari, F.; Moccetti, T.; Vassalli, G. Extracellular Vesicles from Human Cardiac Progenitor Cells Inhibit Cardiomyocyte Apoptosis and Improve Cardiac Function after Myocardial Infarction Cardiovasc. Res. 2014, 103, 530-541 10.1093/cvr/cvu167
70. 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 10.1007/s00109-013-1110-5
71. Timmers, L.; Lim, S. K.; Hoefer, I. E.; Arslan, F.; Lai, R. C.; Van Oorschot, A. A. M.; Goumans, M. J.; Strijder, C.; Sze, S. K.; Choo, A.; Piek, J. J.; Doevendans, P. A.; Pasterkamp, G.; De Kleijn, D. P. V. Human Mesenchymal Stem Cell-Conditioned Medium Improves Cardiac Function Following Myocardial Infarction Stem Cell Res. 2011, 6, 206-214 10.1016/j.scr.2011.01.001
72. Timmers, L.; Lim, S. K.; Arslan, F.; Armstrong, J. S.; Hoefer, I. E.; Doevendans, P. A.; Piek, J. J.; El Oakley, R. M.; Choo, A.; Lee, C. N.; Pasterkamp, G.; De Kleijn, D. P. V. Reduction of Myocardial Infarct Size by Human Mesenchymal Stem Cell Conditioned Medium Stem Cell Res. 2008, 1, 129-137 10.1016/j.scr.2008.02.002
73. He, J.; Wang, Y.; Sun, S.; Yu, M.; Wang, C.; Pei, X.; Zhu, B.; Wu, J.; Zhao, W. Bone Marrow Stem Cells-Derived Microvesicles Protect against Renal Injury in the Mouse Remnant Kidney Model Nephrology 2012, 17, 493-500 10.1111/j.1440-1797.2012.01589.x
74. Gatti, S.; Bruno, S.; Deregibus, M. C.; Sordi, A.; Cantaluppi, V.; Tetta, C.; Camussi, G. Microvesicles Derived from Human Adult Mesenchymal Stem Cells Protect against Ischaemia-Reperfusion-Induced Acute and Chronic Kidney Injury Nephrol., Dial., Transplant. 2011, 26, 1474-1483 10.1093/ndt/gfr015
75. Herrera, M. B.; Fonsato, V.; Gatti, S.; Deregibus, M. C.; Sordi, a.; Cantarella, D.; Calogero, R.; Bussolati, B.; Tetta, C.; Camussi, G. Human Liver Stem Cell-Derived Microvesicles Accelerate Hepatic Regeneration in Hepatectomized Rats J. Cell. Mol. Med. 2010, 14, 1605-1618 10.1111/j.1582-4934.2009.00860.x
76. Reis, L. A.; Borges, F. T.; Simões, M. J.; Borges, A. A.; Sinigaglia-Coimbra, R.; Schor, N. Bone Marrow-Derived Mesenchymal Stem Cells Repaired but Did Not Prevent Gentamicin-Induced Acute Kidney Injury through Paracrine Effects in Rats PLoS One 2012, 7, e44092 10.1371/journal.pone.0044092
77. Bruno, S.; Grange, C.; Collino, F.; Deregibus, M. C.; Cantaluppi, V.; Biancone, L.; Tetta, C.; Camussi, G. Microvesicles Derived from Mesenchymal Stem Cells Enhance Survival in a Lethal Model of Acute Kidney Injury PLoS One 2012, 7, e33115 10.1371/journal.pone.0033115
78. Cantaluppi, V.; Gatti, S.; Medica, D.; Figliolini, F.; Bruno, S.; Deregibus, M. C.; Sordi, A.; Biancone, L.; Tetta, C.; Camussi, G. Microvesicles Derived from Endothelial Progenitor Cells Protect the Kidney from Ischemia-Reperfusion Injury by microRNA-Dependent Reprogramming of Resident Renal Cells Kidney Int. 2012, 82, 412-427 10.1038/ki.2012.105
79. Cantaluppi, V.; Biancone, L.; Figliolini, F.; Beltramo, S.; Medica, D.; Deregibus, M. C.; Galimi, F.; Romagnoli, R.; Salizzoni, M.; Tetta, C.; Segoloni, G. P.; Camussi, G. Microvesicles Derived from Endothelial Progenitor Cells Enhance Neoangiogenesis of Human Pancreatic Islets Cell Transplant. 2012, 21, 1305-1320 10.3727/096368911X627534
80. Li, T.; Yan, Y.; Wang, B.; Qian, H.; Zhang, X.; Shen, L.; Wang, M.; Zhou, Y.; Zhu, W.; Li, W.; Xu, W. Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells Alleviate Liver Fibrosis Stem Cells Dev. 2013, 22, 845-854 10.1089/scd.2012.0395
81. Lee, C.; Mitsialis, S. A.; Aslam, M.; Vitali, S. H.; Vergadi, E.; Konstantinou, G.; Sdrimas, K.; Fernandez-Gonzalez, A.; Kourembanas, S. Exosomes Mediate the Cytoprotective Action of Mesenchymal Stromal Cells on Hypoxia-Induced Pulmonary Hypertension Circulation 2012, 126, 2601-2611 10.1161/CIRCULATIONAHA.112.114173
82. Zhang, S.; Chu, W. C.; Lai, R. C.; Lim, S. K.; Hui, J. H. P.; Toh, W. S. Exosomes Derived from Human Embryonic Mesenchymal Stem Cells Promote Osteochondral Regeneration Osteoarthritis Cartilage 2016, 24, 2135-2140 10.1016/j.joca.2016.06.022
83. Kim, S.-H.; Lechman, E. R.; Bianco, N.; Menon, R.; Keravala, A.; Nash, J.; Mi, Z.; Watkins, S. C.; Gambotto, A.; Robbins, P. D. Exosomes Derived from IL-10-Treated Dendritic Cells Can Suppress Inflammation and Collagen-Induced Arthritis J. Immunol. 2005, 174, 6440-6448 10.4049/jimmunol.174.10.6440
84. Kim, S.-H.; Bianco, N. R.; Shufesky, W. J.; Morelli, A. E.; Robbins, P. D. Effective Treatment of Inflammatory Disease Models with Exosomes Derived from Dendritic Cells Genetically Modified to Express IL-4 J. Immunol. 2007, 179, 2242 10.4049/jimmunol.179.4.2242
85. Headland, S. E.; Jones, H. R.; Norling, L. V.; Kim, A.; Souza, P. R.; Corsiero, E.; Gil, C. D.; Nerviani, A.; Dell'Accio, F.; Pitzalis, C.; Oliani, S. M.; Peretti, M. Neutrophil-Derived Microvesicles Enter Cartilage and Protect the Joint in Inflammatory Arthritis Sci. Transl. Med. 2015, 7, 315ra190 10.1126/scitranslmed.aac5608
86. Zhang, B.; Wang, M.; Gong, A.; Zhang, X.; Wu, X.; Zhu, Y.; Shi, H.; Wu, L.; Zhu, W.; Qian, H.; Xu, W. HucMSC-Exosome Mediated-Wnt4 Signaling Is Required for Cutaneous Wound Healing Stem Cells 2015, 33, 2158-2168 10.1002/stem.1771
87. Wang, L.; Gu, Z.; Zhao, X.; Yang, N.; Wang, F.; Deng, A.; Zhao, S.; Luo, L.; Wei, H.; Guan, L.; Gao, Z.; Li, Y.; Wang, L.; Liu, D.; Gao, C. Extracellular Vesicles Released from Human Umbilical Cord-Derived Mesenchymal Stromal Cells Prevent Life-Threatening Acute Graft-versus-Host Disease in a Mouse Model of Allogeneic Hematopoietic Stem Cell Transplantation Stem Cells Dev. 2016, 25, 1874 10.1089/scd.2016.0107
88. Pivoraite, U.; Jarmalavičiute, A.; Tunaitis, V.; Ramanauskaite, G.; Vaitkuviene, A.; Kašeta, V.; Biziulevičiene, G.; Venalis, A.; Pivoriunas, A. Exosomes from Human Dental Pulp Stem Cells Suppress Carrageenan-Induced Acute Inflammation in Mice Inflammation 2015, 38, 1933-1941 10.1007/s10753-015-0173-6
89. Zhuang, X.; Xiang, X.; Grizzle, W.; Sun, D.; Zhang, S.; Axtell, R. C.; Ju, S.; Mu, J.; Zhang, L.; Steinman, L.; Miller, D.; Zhang, H.-G. 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 10.1038/mt.2011.164
90. 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 10.1038/mt.2010.105
91. Xin, H.; Li, Y.; Liu, Z.; Wang, X.; Shang, X.; Cui, Y.; Zhang, Z. G.; Chopp, M. MiR-133b Promotes Neural Plasticity and Functional Recovery after Treatment of Stroke with Multipotent Mesenchymal Stromal Cells in Rats via Transfer of Exosome-Enriched Extracellular Particles Stem Cells 2013, 31, 2737-2746 10.1002/stem.1409
92. Cooper, J. M.; Wiklander, P. B. O.; Nordin, J. Z.; Al-Shawi, R.; Wood, M. J.; Vithlani, M.; Schapira, A. H. V; Simons, J. P.; El-Andaloussi, S.; Alvarez-Erviti, L. Systemic Exosomal siRNA Delivery Reduced Alpha-Synuclein Aggregates in Brains of Transgenic Mice Mov. Disord. 2014, 29, 1476-1485 10.1002/mds.25978
93. Alvarez-Erviti, L.; Seow, Y.; Yin, H.; Betts, C.; Lakhal, S.; Wood, M. J. A. Delivery of siRNA to the Mouse Brain by Systemic Injection of Targeted Exosomes Nat. Biotechnol. 2011, 29, 341-347 10.1038/nbt.1807
94. Tang, K.; Zhang, Y.; Zhang, H.; Xu, P.; Liu, J.; Ma, J.; Lv, M.; Li, D.; Katirai, F.; Shen, G.-X.; Zhang, G.; Feng, Z.-H.; Ye, D.; Huang, B. Delivery of Chemotherapeutic Drugs in Tumour Cell-Derived Microparticles Nat. Commun. 2012, 3, 1282 10.1038/ncomms2282
95. Mocharla, P.; Briand, S.; Giannotti, G.; Do, C.; Jakob, P.; Paneni, F.; Luscher, T.; Landmesser, U. AngiomiR-126 Expression and Secretion from Circulating CD34+ and CD14+ PBMCs: Role for Proangiogenic Effects and Alterations in Type 2 Diabetics Blood 2013, 121, 226-236 10.1182/blood-2012-01-407106
96. Silva, A. K. A.; Kolosnjaj-Tabi, J.; Bonneau, S.; Marangon, I.; Boggetto, N.; Aubertin, K.; Clement, O.; Bureau, M. F.; Luciani, N.; Gazeau, F.; Wilhelm, C. Magnetic and Photoresponsive Theranosomes: Translating Cell-Released Vesicles into Smart Nanovectors for Cancer Therapy ACS Nano 2013, 7, 4954-4966 10.1021/nn400269x
97. Ohno, S.; Takanashi, M.; Sudo, K.; Ueda, S.; Ishikawa, A.; Matsuyama, N.; Fujita, K.; Mizutani, T.; Ohgi, T.; Ochiya, T.; Gotoh, N.; Kuroda, M. Systemically Injected Exosomes Targeted to EGFR Deliver Antitumor microRNA to Breast Cancer Cells Mol. Ther. 2013, 21, 185-191 10.1038/mt.2012.180
98. Mizrak, A.; Bolukbasi, M. F.; Ozdener, G. B.; Brenner, G. J.; Madlener, S.; Erkan, E. P.; Ströbel, T.; Breakefield, X. O.; Saydam, O. Genetically Engineered Microvesicles Carrying Suicide mRNA/protein Inhibit Schwannoma Tumor Growth Mol. Ther. 2013, 21, 101-108 10.1038/mt.2012.161
99. Tian, Y.; Li, S.; Song, J.; Ji, T.; Zhu, M.; Anderson, G. J.; Wei, J.; Nie, G. A Doxorubicin Delivery Platform Using Engineered Natural Membrane Vesicle Exosomes for Targeted Tumor Therapy Biomaterials 2014, 35, 2383-2390 10.1016/j.biomaterials.2013.11.083
100. 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 10.1038/nm0598-594
101. Viaud, S.; Terme, M.; Flament, C.; Taieb, J.; Andre, F.; Novault, S.; Escudier, B.; Robert, C.; Caillat-Zucman, S.; Tursz, T.; Zitvogel, L.; Chaput, N. Dendritic Cell-Derived Exosomes Promote Natural Killer Cell Activation and Proliferation: A Role for NKG2D Ligands and IL-15Ra PLoS One 2009, 4, e4942 10.1371/journal.pone.0004942
102. Cheng, Y.; Schorey, J. S. Exosomes Carrying Mycobacterial Antigens Can Protect Mice against Mycobacterium Tuberculosis Infection Eur. J. Immunol. 2013, 43, 3279-3290 10.1002/eji.201343727
103. Beauvillain, C.; Juste, M. O.; Dion, S.; Pierre, J.; Dimier-Poisson, I. Exosomes Are an Effective Vaccine against Congenital Toxoplasmosis in Mice Vaccine 2009, 27, 1750-1757 10.1016/j.vaccine.2009.01.022
104. Colino, J.; Snapper, C. M. Exosomes from Bone Marrow Dendritic Cells Pulsed with Diphtheria Toxoid Preferentially Induce Type 1 Antigen-Specific IgG Responses in Naive Recipients in the Absence of Free Antigen J. Immunol. 2006, 177, 3757-3762 10.4049/jimmunol.177.6.3757
105. Del Cacho, E.; Gallego, M.; Lee, S. H.; Lillehoj, H. S.; Quilez, J.; Lillehoj, E. P.; Sánchez-Acedo, C. Induction of Protective Immunity against Eimeria Tenella Infection Using Antigen-Loaded Dendritic Cells (DC) and DC-Derived Exosomes Vaccine 2011, 29, 3818-3825 10.1016/j.vaccine.2011.03.022
106. Keiser, P. B.; Biggs-Cicatelli, S.; Moran, E. E.; Schmiel, D. H.; Pinto, V. B.; Burden, R. E.; Miller, L. B.; Moon, J. E.; Bowden, R. A.; Cummings, J. F.; Zollinger, W. D. A Phase 1 Study of a Meningococcal Native Outer Membrane Vesicle Vaccine Made from a Group B Strain with Deleted lpxL1 and synX, over-Expressed Factor H Binding Protein, Two PorAs and Stabilized OpcA Expression Vaccine 2011, 29, 1413-1420 10.1016/j.vaccine.2010.12.039
107. Morse, M. A.; Garst, J.; Osada, T.; Khan, S.; Hobeika, A.; Clay, T. M.; Valente, N.; Shreeniwas, R.; Sutton, M. A.; Delcayre, A.; Hsu, D.-H.; Le Pecq, J.-B.; Lyerly, H. K. A Phase I Study of Dexosome Immunotherapy in Patients with Advanced Non-Small Cell Lung Cancer J. Transl. Med. 2005, 3, 9 10.1186/1479-5876-3-9
108. Dai, S.; Wei, D.; Wu, Z.; Zhou, X.; Wei, X.; Huang, H.; Li, G. Phase I Clinical Trial of Autologous Ascites-Derived Exosomes Combined with GM-CSF for Colorectal Cancer Mol. Ther. 2008, 16, 782-790 10.1038/mt.2008.1
109. Kordelas, L.; Rebmann, V.; Ludwig, A.-K.; Radtke, S.; Ruesing, J.; Doeppner, T. R.; Epple, M.; Horn, P. A.; Beelen, D. W.; Giebel, B. MSC-Derived Exosomes: A Novel Tool to Treat Therapy-Refractory Graft-versus-Host Disease Leukemia 2014, 28, 970-973 10.1038/leu.2014.41
110. Van Den Boorn, J. G.; Schlee, M.; Coch, C.; Hartmann, G. SiRNA Delivery with Exosome Nanoparticles Nat. Biotechnol. 2011, 29, 325-326 10.1038/nbt.1830
111. LaVan, D. A.; McGuire, T.; Langer, R. Small-Scale Systems for in Vivo Drug Delivery Nat. Biotechnol. 2003, 21, 1184-1191 10.1038/nbt876
112. 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 10.1002/immu.200310028
113. Zomer, A.; Maynard, C.; Verweij, F. J.; Kamermans, A.; Schafer, R.; Beerling, E.; Schiffelers, R. M.; De Wit, E.; Berenguer, J.; Ellenbroek, S. I. J.; Wurdinger, T.; Pegtel, D. M.; Van Rheenen, J. In Vivo Imaging Reveals Extracellular Vesicle-Mediated Phenocopying of Metastatic Behaviour Cell 2015, 161, 1046-1057 10.1016/j.cell.2015.04.042
114. Ridder, K.; Keller, S.; Dams, M.; Rupp, A.-K.; Schlaudraff, J.; Del Turco, D.; Starmann, J.; Macas, J.; Karpova, D.; Devraj, K.; Depboylu, C.; Landfried, B.; Arnold, B.; Plate, K. H.; Hoglinger, G.; Sultmann, H.; Altevogt, P.; Momma, S. Extracellular Vesicle-Mediated Transfer of Genetic Information between the Hematopoietic System and the Brain in Response to Inflammation PLoS Biol. 2014, 12, e1001874 10.1371/journal.pbio.1001874
115. Robbins, P. D. P.; Morelli, A. E. A. Regulation of Immune Responses by Extracellular Vesicles Nat. Rev. Immunol. 2014, 14, 195-208 10.1038/nri3622
116. Lösche, W.; Scholz, T.; Temmler, U.; Oberle, V.; Claus, R. A. Platelet-Derived Microvesicles Transfer Tissue Factor to Monocytes but Not to Neutrophils Platelets 2004, 15, 109-115 10.1080/09537100310001649885
117. Hoshino, A.; Costa-Silva, B.; Shen, T.-L.; Rodrigues, G.; Hashimoto, A.; Tesic Mark, M.; Molina, H.; Kohsaka, S.; Di Giannatale, A.; Ceder, S.; Singh, S.; Williams, C.; Soplop, N.; Uryu, K.; Pharmer, L.; King, T.; Bojmar, L.; Davies, A. E.; Ararso, Y.; Zhang, T. et al. Tumour Exosome Integrins Determine Organotropic Metastasis Nature 2015, 527, 329-335 10.1038/nature15756
118. Wood, M. J. A.; O'Loughlin, A. J.; Lakhal, S. Exosomes and the Blood-Brain Barrier: Implications for Neurological Diseases Ther. Delivery 2011, 2, 1095-1099 10.4155/tde.11.83
119. Armstrong, J. P. K.; Perriman, A. W. Strategies for Cell Membrane Functionalization Exp. Biol. Med. 2016, 241, 1098-1106 10.1177/1535370216650291
120. Armstrong, J. P. K.; Shakur, R.; Horne, J. P.; Dickinson, S. C.; Armstrong, C. T.; Lau, K.; Kadiwala, J.; Lowe, R.; Seddon, A. M.; Mann, S.; Anderson, J. L. R.; Perriman, A. W. P.; Hollander, A. P. Artificial Membrane Binding Proteins Stimulate Oxygenation of Stem Cells during Tissue Engineering of Large Cartilage Constructs Nat. Commun. 2015, 6, 7405 10.1038/ncomms8405
121. Correia Carreira, S.; Armstrong, J. P. K.; Seddon, A. M.; Perriman, A. W.; Hartley-Davies, R.; Schwarzacher, W. Ultra-Fast Stem Cell Labelling Using Cationised Magnetoferritin Nanoscale 2016, 8, 7474-7483 10.1039/C5NR07144E
122. Ridder, K.; Sevko, A.; Heide, J.; Dams, M.; Rupp, A.-K.; Macas, J.; Starmann, J.; Tjwa, M.; Plate, K. H.; Sultmann, H.; Altevogt, P.; Umansky, V.; Momma, S. Extracellular Vesicle-Mediated Transfer of Functional RNA in the Tumor Microenvironment Oncoimmunology 2015, 4, e1008371 10.1080/2162402X.2015.1008371
123. Akao, Y.; Iio, A.; Itoh, T.; Noguchi, S.; Itoh, Y.; Ohtsuki, Y.; Naoe, T. Microvesicle-Mediated RNA Molecule Delivery System Using Monocytes/Macrophages Mol. Ther. 2011, 19, 395-399 10.1038/mt.2010.254
124. 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 10.1074/jbc.M110.107821
125. Luo, S.-S.; Ishibashi, O.; Ishikawa, G.; Ishikawa, T.; Katayama, A.; Mishima, T.; Takizawa, T.; Shigihara, T.; Goto, T.; Izumi, A.; Ohkuchi, A.; Matsubara, S.; Takeshita, T.; Takizawa, T. Human Villous Trophoblasts Express and Secrete Placenta-Specific microRNAs into Maternal Circulation via Exosomes Biol. Reprod. 2009, 81, 717-729 10.1095/biolreprod.108.075481
126. Yang, M.; Chen, J.; Su, F.; Yu, B.; Su, F.; Lin, L.; Liu, Y.; Huang, J.-D.; Song, E. Microvesicles Secreted by Macrophages Shuttle Invasion-Potentiating microRNAs into Breast Cancer Cells Mol. Cancer 2011, 10, 117 10.1186/1476-4598-10-117
127. Zhang, Y.; Liu, D.; Chen, X.; Li, J.; Li, L.; Bian, Z.; Sun, F.; Lu, J.; Yin, Y.; Cai, X.; Qi, S.; Wang, K.; Ba, Y.; Wang, Q.; Wang, D.; Yang, J.; Liu, P.; Xu, T.; Yan, Q.; Zhang, J. et al. Secreted Monocytic miR-150 Enhances Targeted Endothelial Cell Migration Mol. Cell 2010, 39, 133-144 10.1016/j.molcel.2010.06.010
128. Buck, A. H.; Coakley, G.; Simbari, F.; McSorley, H. J.; Quintana, J. F.; Le Bihan, T.; Kumar, S.; Abreu-Goodger, C.; Lear, M.; Harcus, Y.; Ceroni, A.; Babayan, S. A.; Blaxter, M.; Ivens, A.; Maizels, R. M. Exosomes Secreted by Nematode Parasites Transfer Small RNAs to Mammalian Cells and Modulate Innate Immunity Nat. Commun. 2014, 5, 5488 10.1038/ncomms6488
129. Pegtel, D. M.; Cosmopoulos, K.; Thorley-Lawson, D. A.; Van Eijndhoven, M. A. J.; Hopmans, E. S.; Lindenberg, J. L.; De Gruijl, T. D.; Würdinger, T.; Middeldorp, J. M. Functional Delivery of Viral miRNAs via Exosomes Proc. Natl. Acad. Sci. U. S. A. 2010, 107, 6328-6333 10.1073/pnas.0914843107
130. 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 10.1016/j.mcn.2011.12.001
131. Pan, Q.; Ramakrishnaiah, V.; Henry, S.; Fouraschen, S.; De Ruiter, P. E.; Kwekkeboom, J.; Tilanus, H. W.; Janssen, H. L. A.; Van Der Laan, L. J. W. Hepatic Cell-to-Cell Transmission of Small Silencing RNA Can Extend the Therapeutic Reach of RNA Interference (RNAi) Gut 2012, 61, 1330-1339 10.1136/gutjnl-2011-300449
132. Tkach, M.; Thery, C. Communication by Extracellular Vesicles: Where We Are and Where to Go Cell 2016, 164, 1226-1232 10.1016/j.cell.2016.01.043
133. Lötvall, J.; Hill, A. F.; Hochberg, F.; Buzás, E. I.; Di Vizio, D.; Gardiner, C.; Gho, Y. S.; Kurochkin, I. V.; Mathivanan, S.; Quesenberry, P.; Sahoo, S.; Tahara, H.; Wauben, M. H.; Witwer, K. W.; Thery, C. Minimal Experimental Requirements for Definition of Extracellular Vesicles and Their Functions: A Position Statement from the International Society for Extracellular Vesicles J. Extracell. Vesicles 2014, 3, 26913 10.3402/jev.v3.26913
134. Kanada, M.; Bachmann, M. H.; Hardy, J. W.; Omar, D.; Bronsart, L.; Wang, A.; Sylvester, M. D.; Schmidt, T. L.; Kaspar, R. L.; Butte, M. J.; Matin, A. C.; Contag, C. H. Differential Fates of Biomolecules Delivered to Target Cells via Extracellular Vesicles Proc. Natl. Acad. Sci. U. S. A. 2015, 1433-1442 10.1073/pnas.1418401112
135. 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 Genomics 2011, 12, S18 10.1186/1471-2164-12-S3-S18
136. 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 10.1038/mtna.2011.2
137. Hassuna, N.; Monk, P. N.; Moseley, G. W.; Partridge, L. J. Strategies for Targeting Tetraspanin Proteins Potential Therapeutic Applications in Microbial Infections BioDrugs 2009, 23, 341-359 10.2165/11315650-000000000-00000
138. Stickney, Z.; Losacco, J.; McDevitt, S.; Zhang, Z.; Lu, B. Development of Exosome Surface Display Technology in Living Human Cells Biochem. Biophys. Res. Commun. 2016, 472, 53-59 10.1016/j.bbrc.2016.02.058
139. Suetsugu, A.; Honma, K.; Saji, S.; Moriwaki, H.; Ochiya, T.; Hoffman, R. M. Imaging Exosome Transfer from Breast Cancer Cells to Stroma at Metastatic Sites in Orthotopic Nude-Mouse Models Adv. Drug Delivery Rev. 2013, 65, 383-390 10.1016/j.addr.2012.08.007
140. Takahashi, Y.; Nishikawa, M.; Shinotsuka, H.; Matsui, Y.; Ohara, S.; Imai, T.; Takakura, Y. Visualization and in Vivo Tracking of the Exosomes of Murine Melanoma B16-BL6 Cells in Mice after Intravenous Injection J. Biotechnol. 2013, 165, 77-84 10.1016/j.jbiotec.2013.03.013
141. Lai, C. P.; Kim, E. Y.; Badr, C. E.; Weissleder, R.; Mempel, T. R.; Tannous, B. a; Breakefield, X. O. Visualization and Tracking of Tumour Extracellular Vesicle Delivery and RNA Translation Using Multiplexed Reporters Nat. Commun. 2015, 6, 7029 10.1038/ncomms8029
142. El-Andaloussi, S.; Lee, Y.; Lakhal-Littleton, S.; Li, J.; Seow, Y.; Gardiner, C.; Alvarez-Erviti, L.; Sargent, I. L.; Wood, M. J. A. Exosome-Mediated Delivery of siRNA in Vitro and in Vivo Nat. Protoc. 2012, 7, 2112-2126 10.1038/nprot.2012.131
143. Hung, M. E.; Leonard, J. N. Stabilization of Exosome-Targeting Peptides via Engineered Glycosylation J. Biol. Chem. 2015, 290, 8166-8172 10.1074/jbc.M114.621383
144. Kooijmans, S. A. A.; Aleza, C. G.; Roffler, S. R.; Van Solinge, W. W.; Vader, P.; Schiffelers, R. M. Display of GPI-Anchored Anti-EGFR Nanobodies on Extracellular Vesicles Promotes Tumour Cell Targeting J. Extracell. Vesicles 2016, 5, 31053 10.3402/jev.v5.31053
145. Delcayre, A.; Estelles, A.; Sperinde, J.; Roulon, T.; Paz, P.; Aguilar, B.; Villanueva, J.; Khine, S. S.; Le Pecq, J. B. Exosome Display Technology: Applications to the Development of New Diagnostics and Therapeutics Blood Cells, Mol., Dis. 2005, 35, 158-168 10.1016/j.bcmd.2005.07.003
146. Hartman, Z. C.; Wei, J.; Glass, O. K.; Guo, H.; Lei, G.; Yang, X. Y.; Osada, T.; Hobeika, A.; Delcayre, A.; Le Pecq, J. B.; Morse, M. A.; Clay, T. M.; Lyerly, H. K. Increasing Vaccine Potency through Exosome Antigen Targeting Vaccine 2011, 29, 9361-9367 10.1016/j.vaccine.2011.09.133
147. Rountree, R. B.; Mandl, S. J.; Nachtwey, J. M.; Dalpozzo, K.; Do, L.; Lombardo, J. R.; Schoonmaker, P. L.; Brinkmann, K.; Dirmeier, U.; Laus, R.; Delcayre, A. Exosome Targeting of Tumor Antigens Expressed by Cancer Vaccines Can Improve Antigen Immunogenicity and Therapeutic Efficacy Cancer Res. 2011, 71, 5235-5244 10.1158/0008-5472.CAN-10-4076
148. Maguire, C. A.; Balaj, L.; Sivaraman, S.; Crommentuijn, M. H. W.; Ericsson, M.; Mincheva-Nilsson, L.; Baranov, V.; Gianni, D.; Tannous, B. A.; Sena-Esteves, M.; Breakefield, X. O.; Skog, J. Microvesicle-Associated AAV Vector as a Novel Gene Delivery System Mol. Ther. 2012, 20, 960-971 10.1038/mt.2011.303
149. Kooijmans, S. A. A.; Stremersch, S.; Braeckmans, K.; De Smedt, S. C.; Hendrix, A.; Wood, M. J. A.; Schiffelers, R. M.; Raemdonck, K.; Vader, P. Electroporation-Induced siRNA Precipitation Obscures the Efficiency of siRNA Loading into Extracellular Vesicles J. Controlled Release 2013, 172, 229-238 10.1016/j.jconrel.2013.08.014
150. Keppler, O. T.; Stehling, P.; Herrmann, M.; Kayser, H.; Grunow, D.; Reutter, W.; Pawlita, M. Biosynthetic Modulation of Sialic Acid-Dependent Virus-Receptor Interactions of Two Primate Polyoma Viruses J. Biol. Chem. 1995, 270, 1308-1314 10.1074/jbc.270.3.1308
151. Du, J.; Che, P.-L.; Wang, Z.-Y.; Aich, U.; Yarema, K. J. Designing a Binding Interface for Control of Cancer Cell Adhesion via 3D Topography and Metabolic Oligosaccharide Engineering Biomaterials 2011, 32, 5427-5437 10.1016/j.biomaterials.2011.04.005
152. Juillerat, F. K.; Borcard, F.; Staedler, D.; Scaletta, C.; Applegate, L. A.; Comas, H.; Gauckler, L. J.; Gerber-Lemaire, S.; Juillerat-Jeanneret, L.; Gonzenbach, U. T. Functionalization of Microstructured Open-Porous Bioceramic Scaffolds with Human Fetal Bone Cells Bioconjugate Chem. 2012, 23, 2278-2290 10.1021/bc300407x
153. Wang, M.; Altinoglu, S.; Takeda, Y. S.; Xu, Q. Integrating Protein Engineering and Bioorthogonal Click Conjugation for Extracellular Vesicle Modulation and Intracellular Delivery PLoS One 2015, 10, e0141860 10.1371/journal.pone.0141860
154. Mahal, L. K.; Yarema, K. J.; Bertozzi, C. R. Engineering Chemical Reactivity on Cell Surfaces through Oligosaccharide Biosynthesis Science 1997, 276, 1125-1128 10.1126/science.276.5315.1125
155. Okeley, N. M.; Toki, B. E.; Zhang, X.; Je, S. C.; Burke, P. J.; Alley, S. C.; Senter, P. D. Metabolic Engineering of Monoclonal Antibody Carbohydrates for Antibody-Drug Conjugation Bioconjugate Chem. 2013, 24, 1650 10.1021/bc4002695
156. Iwasaki, Y.; Matsunaga, A.; Fujii, S. Preparation of Biointeractive Glycoprotein-Conjugated Hydrogels through Metabolic Oligosacchalide Engineering Bioconjugate Chem. 2014, 25, 1626-1631 10.1021/bc5003295
157. Neubert, J.; Glumm, J. Promoting Neuronal Regeneration Using Extracellular Vesicles Loaded with Superparamagnetic Iron Oxide Nanoparticles Neural Regener. Res. 2016, 11, 61-63 10.4103/1673-5374.175043
158. Silva, A. K. A.; Luciani, N.; Gazeau, F.; Aubertin, K.; Bonneau, S.; Chauvierre, C.; Letourneur, D.; Wilhelm, C. Combining Magnetic Nanoparticles with Cell Derived Microvesicles for Drug Loading and Targeting Nanomedicine 2015, 11, 645-655 10.1016/j.nano.2014.11.009
159. Tatischeff, I.; Alfsen, A. A New Biological Strategy for Drug Delivery: Eucaryotic Cell-Derived Nanovesicles J. Biomater. Nanobiotechnol. 2011, 2, 494-499 10.4236/jbnb.2011.225060
160. Peterson, B. R. Synthetic Mimics of Mammalian Cell Surface Receptors: Prosthetic Molecules That Augment Living Cells Org. Biomol. Chem. 2005, 3, 3607-3612 10.1039/b509866a
161. Sarkar, D.; Vemula, P. K.; Zhao, W.; Gupta, A.; Karnik, R.; Karp, J. M. Engineered Mesenchymal Stem Cells with Self-Assembled Vesicles for Systemic Cell Targeting Biomaterials 2010, 31, 5266-5274 10.1016/j.biomaterials.2010.03.006
162. Lee, J.; Lee, H.; Goh, U.; Kim, J.; Jeong, M.; Lee, J.; Park, J.-H. Cellular Engineering with Membrane Fusogenic Liposomes to Produce Functionalized Extracellular Vesicles ACS Appl. Mater. Interfaces 2016, 8, 6790-6795 10.1021/acsami.6b01315
163. Barenholz, Y. Liposome Application: Problems and Prospects Curr. Opin. Colloid Interface Sci. 2001, 6, 66-77 10.1016/S1359-0294(00)00090-X
164. Smyth, T. J.; Petrova, K.; Payton, N. M.; Persaud, I.; Redzic, J. S.; Graner, M.; Smith-Jones, P.; Anchordoquy, T. J. Surface Functionalization of Exosomes Using Click Chemistry Bioconjugate Chem. 2014, 25, 1777-1784 10.1021/bc500291r
165. AK, D. Chemical Bonding and Structure. In A Text Book of Inorganic Chemistry; New Age International Limited: New Delhi, 2003.
166. Berg, J.; Tymoczko, J.; Stryer, L. Chemical Bonds in Biochemistry. In Biochemistry; W. H. Freeman: New York, 2002.
167. Nakase, I.; Futaki, S. Combined Treatment with a pH-Sensitive Fusogenic Peptide and Cationic Lipids Achieves Enhanced Cytosolic Delivery of Exosomes Sci. Rep. 2015, 5, 10112 10.1038/srep10112
168. Nel, A. E.; Mädler, L.; Velegol, D.; Xia, T.; Hoek, E. M. V; Somasundaran, P.; Klaessig, F.; Castranova, V.; Thompson, M. Understanding Biophysicochemical Interactions at the Nano-Bio Interface Nat. Mater. 2009, 8, 543-557 10.1038/nmat2442
169. Qi, H.; Liu, C.; Long, L.; Ren, Y.; Zhang, S.; Chang, X.; Qian, X.; Jia, H.; Zhao, J.; Sun, J.; Hou, X.; Yuan, X.; Kang, C. Blood Exosomes Endowed with Magnetic and Targeting Properties for Cancer Therapy ACS Nano 2016, 10, 3323-3333 10.1021/acsnano.5b06939
170. Parolini, I.; Federici, C.; Raggi, C.; Lugini, L.; Palleschi, S.; De Milito, A.; Coscia, C.; Iessi, E.; Logozzi, M.; Molinari, A.; Colone, M.; Tatti, M.; Sargiacomo, M.; Fais, S. Microenvironmental pH Is a Key Factor for Exosome Traffic in Tumor Cells J. Biol. Chem. 2009, 284, 34211-34222 10.1074/jbc.M109.041152
171. Sato, Y. T.; Umezaki, K.; Sawada, S.; Mukai, S.-A.; Sasaki, Y.; Harada, N.; Shiku, H.; Akiyoshi, K. Engineering Hybrid Exosomes by Membrane Fusion with Liposomes Sci. Rep. 2016, 6, 21933 10.1038/srep21933
172. Kooijmans, S. A.; Fliervoet, L. A. L.; Van Der Meel, R.; Fens, M. H. A. M.; Heijnen, H. F. G.; Van Bergen En Henegouwen, P. M. P.; Vader, P.; Schiffelers, R. M. PEGylated and Targeted Extracellular Vesicles Display Enhanced Cell Specificity and Circulation Time J. Controlled Release 2016, 224, 77-85 10.1016/j.jconrel.2016.01.009
173. Fuhrmann, G.; Serio, A.; Mazo, M.; Nair, R.; Stevens, M. M. Active Loading into Extracellular Vesicles Significantly Improves the Cellular Uptake and Photodynamic Effect of Porphyrins J. Controlled Release 2015, 205, 35-44 10.1016/j.jconrel.2014.11.029
174. Harp, D.; Driss, A.; Mehrabi, S.; Chowdhury, I.; Xu, W.; Liu, D.; Garcia-Barrio, M.; Taylor, R. N.; Gold, B.; Jefferson, S.; Sidell, N.; Thompson, W. Exosomes Derived from Endometriotic Stromal Cells Have Enhanced Angiogenic Effects in Vitro Cell Tissue Res. 2016, 365, 187-196 10.1007/s00441-016-2358-1
175. Nicola, A. M.; Frases, S.; Casadevall, A. Lipophilic Dye Staining of Cryptococcus Neoformans Extracellular Vesicles and Capsule Eukaryotic Cell 2009, 8, 1373-1380 10.1128/EC.00044-09
176. Maas, S. L. N.; De Vrij, J.; Van Der Vlist, E. J.; Geragousian, B.; Van Bloois, L.; Mastrobattista, E.; Schiffelers, R. M.; Wauben, M. H. M.; Broekman, M. L. D.; Nolte-'T Hoen, E. N. M. Possibilities and Limitations of Current Technologies for Quantification of Biological Extracellular Vesicles and Synthetic Mimics J. Controlled Release 2015, 200, 87-96 10.1016/j.jconrel.2014.12.041
177. Smyth, T.; Kullberg, M.; Malik, N.; Smith-Jones, P.; Graner, M. W.; Anchordoquy, T. J. Biodistribution and Delivery Efficiency of Unmodified Tumor-Derived Exosomes J. Controlled Release 2015, 199, 145-155 10.1016/j.jconrel.2014.12.013
178. Yang, T.; Martin, P.; Fogarty, B.; Brown, A.; Schurman, K.; Phipps, R.; Yin, V. P.; Lockman, P.; Bai, S. Exosome Delivered Anticancer Drugs across the Blood-Brain Barrier for Brain Cancer Therapy in Danio Rerio Pharm. Res. 2015, 32, 2003-2014 10.1007/s11095-014-1593-y
179. Wahlgren, J.; Karlson, T. D. L.; Brisslert, M.; Sani, F. V.; Telemo, E.; Sunnerhagen, P.; Valadi, H. Plasma Exosomes Can Deliver Exogenous Short Interfering RNA to Monocytes and Lymphocytes Nucleic Acids Res. 2012, 40, e130 10.1093/nar/gks463
180. Hood, J. L.; Scott, M. J.; Wickline, S. A. Maximizing Exosome Colloidal Stability Following Electroporation Anal. Biochem. 2014, 448, 41-49 10.1016/j.ab.2013.12.001
181. Wassler, M.; Jonasson, I.; Persson, R.; Fries, E. Differential Permeabilization of Membranes by Saponin Treatment of Isolated Rat Hepatocytes Release of Secretory Proteins Biochem. J. 1987, 247, 407-415 10.1042/bj2470407
182. Gutiérrez Millán, C.; Castañeda, A. Z.; Sayalero Marinero, M. L.; Lanao, J. M. Factors Associated with the Performance of Carrier Erythrocytes Obtained by Hypotonic Dialysis Blood Cells, Mol., Dis. 2004, 33, 132-140 10.1016/j.bcmd.2004.06.004
183. Yim, N.; Ryu, S.; Choi, K.; Lee, K. R.; Lee, S.; Choi, H.; Kim, J.; Shaker, M. R.; Sun, W.; Park, J.; Kim, D.; Heo, W. D.; Choi, C. Exosome Engineering for Efficient Intracellular Delivery of Soluble Proteins Using Optically Reversible Protein-Protein Interaction Module Nat. Commun. 2016, 7, 12277 10.1038/ncomms12277