Exosome platform for diagnosis and monitoring of traumatic brain injury

Philosophical Transactions of the Royal Society B: Biological Sciences

Volumn 369, Issue 1652, 2014, Pages

  Taylor, Douglas D ^a   Gercel Taylor, Cicek ^a  

^a Exosome Sciences Inc   (United States)

Author keywords

Cytokines; Exosomes; Inflammatory response; Neurodegeneration; Traumatic brain injury

Indexed keywords

BRAIN; CELL ORGANELLE; HEALTH RISK; INJURY;

BIOLOGICAL MARKER; CYTOKINE;

BLOOD; BRAIN INJURIES; CELL COMMUNICATION; EXOSOME; HUMAN; IMMUNOLOGY; INFLAMMATION; NEUROLOGIC EXAMINATION; PHYSIOLOGY;

BIOLOGICAL MARKERS; BRAIN INJURIES; CELL COMMUNICATION; CYTOKINES; DIAGNOSTIC TECHNIQUES, NEUROLOGICAL; EXOSOMES; HUMANS; INFLAMMATION;

EID: 84906078522     PISSN: 09628436     EISSN: 14712970     Source Type: Journal    
DOI: 10.1098/rstb.2013.0503     Document Type: Review

References (99)

1. Faul M, Xu L, Wald MM, Coronado VG. 2010 Traumatic brain injury in the United States: emergency department visits, hospitalizations and deaths 2002-2006. Atlanta, GA, USA: Centers for Disease Control and Prevention, National Center for Injury Prevention and Control.
2. Coronado VG, Xu L, Basavaraju SV, Mcguire LC, Wald MM, Faul MD, Guzman BR, Hemphill JD. 2011 Surveillance for traumatic brain injury-related deaths-United States, 1997-2007. MMWR Surveill. Summ. 60, 1-32.
3. W.H. Organization. 2006 Neurological disorders: public health challenges. Geneva, Switzerland: WHO Press.
4. Taylor BC, Hagel EM, Carlson KF, Cifu DX, Cutting A, Bidelspach DE, Sayer NA. 2012 Prevalence and costs of co-occurring traumatic brain injury with and without psychiatric disturbance and pain among Afghanistan and Iraq War Veteran V.A. users. Med. Care 50, 342-346. (doi:10.1097/MLR.0b013e3182 45a558)
5. Schwab KA, Ivins B, Cramer G, Johnson W, Sluss-Tiller M, Kiley K, Lux W, Warden D. 2007 Screening for traumatic brain injury in troops returning from deployment in Afghanistan and Iraq: initial investigation of the usefulness of a short screening tool for traumatic brain injury. J. Head Trauma Rehabil. 22, 377-389. (doi:10.1097/01.HTR.0000 300233.98242.87)
6. MacDonald CL et al. 2011 Detection of blast-related traumatic brain injury in U.S. military personnel. N. Engl. J. Med. 364, 2091-2100. (doi:10.1056/ NEJMoa1008069)
7. Svetlov SI, Larner SF, Kirk DR, Atkinson J, Hayes RL, Wang KKW. 2009 Biomarkers of blast-induced neurotrauma: profiling molecular and cellular mechanisms of blast brain injury. J. Neurotrauma 26, 913-921. (doi:10.1089/neu.2008.0609)
8. Maas AI, Stocchetti N, Bullock R. 2008 Moderate and severe traumatic brain injury in adults. Lancet Neurol. 7, 728-741. (doi:10.1016/S1474-4422(08) 70164-9)
9. Kochanek PM, Bramlett H, Dietrich WD, Dixon CE, Hayes RL, Povlishock J, Tortella FC, Wang KK. 2011 A novel multicenter preclinical drug screening and biomarker consortium for experimental traumatic brain injury: operation brain trauma therapy. J. Trauma 71, S15-S24. (doi:10.1097/TA. 0b013e31822117fe)
10. Thornhill S et al. 2000 Disability in young people and adults one year after head injury: prospective cohort study. Br. Med. J. 320, 1631-1635. (doi:10. 1136/bmj.320.7250.1631)
11. Popovich PG, Longbrake EE. 2008 Can the immune system be harnessed to repair the CNS? Nat. Rev. Neurosci. 9, 481-493. (doi:10.1038/nrn2398)
12. Fehlings MG, Nguyen DH. 2010 Immunoglobulin G: a potential treatment to attenuate neuroinflammation following spinal cord injury. J. Clin. Immunol. 1, S109-S112. (doi:10.1007/s10875-010-9404-7)
13. Schwartz M, Butovsky O, Bruck W, Hanisch UK. 2006 Microglial phenotype: is the commitment reversible? Trends Neurosci. 29, 68-74. (doi:10.1016/j.tins.2005. 12.005)
14. Bareyre FM, Schwab ME. 2003 Inflammation, degeneration and regeneration in the injured spinal cord: insights from DNA microarrays. Trends Neurosci. 26, 555-563. (doi:10.1016/j.tins.2003.08.004)
15. Schnell L, Fearn S, Klassen H, Schwab ME, Perry VH. 1999 Acute inflammatory responses to mechanical lesions in the CNS: differences between brain and spinal cord. Eur. J. Neurosci. 11, 3648-3658. (doi:10.1046/j.1460-9568.1999.00792.x)
16. Anderson AJ. 2002 Mechanisms and pathways of inflammatory responses in CNS trauma: spinal cord injury. J. Spinal Cord Med. 25, 70-79.
17. Gercel-Taylor C, Tullis RH, Atay S, Kesimer M, Taylor DD. 2012 Nanoparticle analysis of circulating cellderived vesicles in ovarian cancer patients. Anal. Biochem. 428, 44-53. (doi:10.1016/j.ab.2012.06.004)
18. Esteller M. 2011 Non-coding RNAs in human disease. Nat. Rev. Genet. 12, 861-874. (doi:10. 1038/nrg3074)
19. Sibley CR, Wood MJ. 2011 The miRNA pathway in neurological and skeletal muscle disease: implications for pathogenesis and therapy. J. Mol. Med. (Berl). 89, 1065-1077. (doi:10.1007/s00109-011-0781-z)
20. Rasouli J, Lekhraj R, White NM, Flamm ES, Pilla AA, Strauch B, Casper D. 2012 Attenuation of interleukin-1beta by pulsed electromagnetic fields after traumatic brain injury. Neurosci. Lett. 519, 4-8. (doi:10.1016/j.neulet.2012.03.089)
21. Adamczak S, Dale G, DeRivero Vaccari JP, Bullock MR, Dietrich WD, Keane RW. 2012 Inflammasome proteins in cerebrospinal fluid of brain-injured patients as markers of functional outcome. J. Neurosurg. 117, 1119-1125. (doi:10.3171/2012. 9.JNS12815)
22. Frugier T, Morganti-Kossmann MC, O'Reilly D, McLean CA. 2010 In situ detection of inflammatory mediators in post mortem human brain tissue after traumatic injury. J. Neurotrauma 27, 497-507. (doi:10.1089/neu.2009.1120)
23. Unterberg AW, Stover J, Kress B, Kiening KL. 2004 Edema and brain trauma. Neuroscience 129, 1021-1029. (doi:10.1016/j.neuroscience.2004.06.046)
24. Woodcock T, Morganti-Kossmann MC. 2013 The role of markers of inflammation in traumatic brain injury. Front Neurol. 4, 18. (doi:10.3389/fneur.2013. 00018)
25. Zhu GW, Wang F, Liu WG. 2009 Classification and prediction of outcome in traumatic brain injury based on computed tomographic imaging. J. Int. Med. Res. 37, 983-995. (doi:10.1177/1473230009 03700402)
26. Xu J, Rasmussen IA, Lagopoulos J, Haberg A. 2007 Diffuse axonal injury in severe traumatic brain injury visualized using high-resolution diffusion tensor imaging. J. Neurotrauma 24, 753-765. (doi:10. 1089/neu.2006.0208)
27. Smith DH, David F, Meaney DF. 2000 Axonal damage in traumatic brain injury. Neuroscientist 6, 483-495. (doi:10.1177/107385840000600611)
28. Taylor DD, Doellgast GJ. 1979 Quantitation of peroxidase-antibody binding to membrane fragments using column chromatography. Anal. Biochem. 98, 53-59. (doi:10.1016/0003-2697(79)90704-8)
29. Taylor DD, Gercel-Taylor C. 2011 Exosomes/ microvesicles: mediators of cancer-associated immunosuppressive microenvironments. Sem. Immunopathol. 33, 441-454. (doi:10.1007/s00281-010-0234-8)
30. Peinado H et al. 2012 Melanoma exosomes educate bone marrow progenitor cells toward a prometastatic phenotype through MET. Nat. Med. 18, 883-891. (doi:10.1038/nm.2753)
31. Trams EG, Lauter CJ, Salem Jr C, Heine U. 1981 Exfoliation of membrane ecto-enzymes in the form of microvesicles. Biochim. Biophys. Acta 645, 63-70. (doi:10.1016/0005-2736(81)90512-5)
32. Zumaquero E et al. 2010 Exosomes from human lymphoblastoid B cells express enzymatically active CD38 that is associated with signaling complexes containing CD81, Hsc-70, and Lyn. Exp. Cell Res. 316, 2692-2706. (doi:10.1016/j.yexcr.2010.05.032)
33. Admyre C, Telemo E, Almqvist N, Lotvall J, Lahesmaa R, Scheynius A, Gabrielsson S. 2008 Exosomes-nanovesicles with possible roles in allergy inflammation. Allergy 63, 404-408. (doi:10. 1111/j.1398-9995.2007.01600.x)
34. Montecalvo A et al. 2008 Exosomes as a short-range mechanism to spread alloantigen between dendritic cells during T cell allorecognition. J. Immunol. 180, 3081-3090. (doi:10.4049/jimmunol.180.5.3081)
35. Rak J. 2010 Microparticles in cancer. Semin. Thromb. Hemost. 36, 888-906. (doi:10.1055/s-0030-1267043)
36. Anand PK. 2010 Exosomal membrane molecules are potent immune response modulators. Commun. Integr. Biol. 3, 405-408. (doi:10.4161/cib.3.5. 12474)
37. Kesimer M, Scull M, Brighton B, DeMaria G, Burns K, O'Neal W, Pickles RJ, Sheehan JK. 2009 Characterization of exosome-like vesicles released from human tracheobronchial ciliated epithelium: a possible role in innate defense. FASEB J. 23, 1858-1868. (doi:10.1096/fj.08-119131)
38. Taylor DD, Gercel-Taylor C. 2013 The origin, function and diagnostic potential of RNA within extracellular vesicles present in human biological fluids. Front. Genet. 4, 0142. (doi:10.3389/fgene.2013.00142)
39. Graner MW et al. 2013 Circulating exosomes as new biomarkers for brain disease and injury. In Proc. SPIE 8723, Sensing Technologies for Global Health, Military Medicine, and Environmental Monitoring III, 87230R. Baltimore, MD, USA. (doi:10.1117/12.2027435)
40. Taylor DD, Gercel-Taylor C. 2008 MicroRNA signatures of tumor-derived exosomes as diagnostic biomarkers of ovarian cancer. Gynecol. Oncol. 110, 13-21. (doi:10.1016/j.ygyno.2008.04.033)
41. Atay S, Gercel-Taylor C, Suttles J, Mor G, Taylor DD. 2011 Trophoblast derived exosomes mediate monocyte recruitment and differentiation. Am. J. Reprod. Immunol. 65, 65-77. (doi:10.1111/j. 1600-0897.2010.00880.x)
42. Kamm K, Vanderkolk W, Lawrence C, Jonker M, Davis AT. 2006 The effect of traumatic brain injury upon the concentration and expression of interleukin-1beta and interleukin-10 in the rat. J. Trauma 60, 152-157. (doi:10.1097/01.ta. 0000196345.81169.a1)
43. Kuhlow CJ, Krady JK, Basu A, Levison SW. 2003 Astrocytic ceruloplasmin expression, which is induced by IL-1b and by traumatic brain injury, increases in the absence of the IL-1 type 1 receptor. Glia 44, 76-84. (doi:10.1002/glia.10273)
44. Kochanek PM, Berger RP, Bayr H, Wagner AK, Jenkins LW, Clark RS. 2008 Biomarkers of primary and evolving damage in traumatic and ischemic brain injury: diagnosis, prognosis, probing mechanisms, and therapeutic decision making. Curr. Opin. Crit. Care 14, 135-141. (doi:10.1097/MCC. 0b013e3282f57564)
45. Youn YA, Kim SJ, Sung IK, Chung SY, Kim YH, Lee IG. 2012 Serial examination of serum IL-8, IL-10 and IL-1Ra levels is significant in neonatal seizures induced by hypoxic-ischaemic encephalopathy. Scand. J. Immunol. 76, 286-293. (doi:10.1111/j.1365-3083. 2012.02710.x)
46. Pan BT, Blostein R, Johnstone RM. 1983 Loss of the transferrin receptor during the maturation of sheep reticulocytes in vitro: an immunological approach. Biochem. J. 210, 37-47.
47. Johnstone RM, Adam M, Hammond JR, Orr L, Turbide C. 1987 Vesicle formation during reticulocyte maturation. Association of plasma membrane activities with released vesicles (exosomes). J. Biol. Chem. 262, 9412-9420.
48. Marhaba R, Klingbeil P, Nuebel T, Nazarenko I, Buechler MW, Zoeller M. 2008 CD44 and EpCAM: cancer-initiating cell markers. Curr. Mol. Med. 8, 784-804. (doi:10.2174/156652408786733667)
49. Park JE, Tan HS, Datta A, Lai RC, Zhang H, Meng W, Lim SK, Sze SK. 2010 Hypoxic tumor cell modulates its microenvironment to enhance angiogenic and metastatic potential by secretion of proteins and exosomes. Mol. Cell Proteomics 9, 1085-1099. (doi:10.1074/mcp.M900381-MCP200)
50. Hong BS et al. 2009 Colorectal cancer cell-derived microvesicles are enriched in cell cycle-related mRNAs that promote proliferation of endothelial cells. BMC Genomics 10, 556. (doi:10.1186/1471-2164-10-556)
51. Xiang X et al. 2009 Induction of myeloid-derived suppressor cells by tumor exosomes. Int. J. Cancer 124, 2621-2633. (doi:10.1002/ijc.24249)
52. Nazarenko I, Rana S, Baumann A, McAlear J, Hellwig A, Trendelenburg M, Lochnit G, Preissner KT, Zöller M. 2010 Cell surface tetraspanin Tspan8 contributes to molecular pathways of exosomeinduced endothelial cell activation. Cancer Res. 70, 1668-1678. (doi:10.1158/0008-5472.CAN-09-2470)
53. Keller S, König AK, Marmé F, Runz S, Wolterink S, Koensgen D, Mustea A, Sehouli J, Altevogt P. 2009 Systemic presence and tumor-growth promoting effect of ovarian carcinoma released exosomes. Cancer Lett. 278, 73-81. (doi:10.1016/j.canlet.2008.12.028)
54. Dolo V, D'Ascenzo S, Violini S, Pompucci L, Festuccia C, Ginestra A, Vittorelli ML, Canevari S, Pavan A. 1999 Matrix-degrading proteinases are shed in membrane vesicles by ovarian cancer cells in vivo and in vitro. Clin. Exp. Metastasis 17, 131-140. (doi:10.1023/A:1006500406240)
55. Dolo V, Ginestra A, Cassara D, Ghersi G, Nagase H, Vittorelli ML. 1999 Shed membrane vesicles and selective localization of gelatinases and MMP-9/ TIMP-1 complexes. Ann. N Y Acad. Sci. 878, 497-499. (doi:10.1111/j.1749-6632.1999.tb07707.x)
56. Graves LE, Ariztia EV, Navari JR, Matzel HJ, Stack MS, Fishman DA. 2004 Proinvasive properties of ovarian cancer ascites-derived membrane vesicles. Cancer Res. 64, 7045-7049. (doi:10.1158/0008-5472.CAN-04-1800)
57. Lewis CE, Pollard JW. 2006 Distinct role of macrophages in different tumor microenvironments. Cancer Res. 66, 605-612. (doi:10.1158/0008-5472. CAN-05-4005)
58. Whiteside TL. 2013 Immune modulation of T-cell and NK (natural killer) cell activities by TEXs (tumour derived exosomes). Biochem. Soc. Trans. 41, 245-251. (doi:10.1042/BST20120265)
59. Atay S, Gercel-Taylor C, Kesimer M, Taylor DD. 2011 Morphologic and proteomic characterization of exosomes released by cultured extravillous trophoblast cells. Exp. Cell Res. 317, 1192-1202. (doi:10.1016/j.yexcr.2011.01.014)
60. Atay S, Roberson C, Gercel-Taylor C, Taylor DD. 2013 Ovarian cancer patient-derived exosomal fibronectin induces pro-inflammatory IL-1b production by macrophages. Exosomes and Microvesicles 1, 1. (doi:10.5772/56180)
61. McLellan AD. 2009 Exosome release by primary B cells. Crit. Rev. Immunol. 29, 203-217. (doi:10. 1615/CritRevImmunol.v29.i3.20)
62. Ratajczak J, Wysoczynski M, Hayek F, Janowska-Wieczorek A, Ratajczak MZ. 2006 Membrane-derived microvesicles: important and underappreciated mediators of cell-to-cell communication. Leukemia 20, 1487-1495. (doi:10.1038/sj.leu.2404296)
63. Ichim TE et al. 2008 Exosomes as a tumor immune escape mechanism: possible therapeutic implications. J. Transl. Med. 6, 37. (doi:10.1186/1479-5876-6-37)
64. Al-Nedawi K, Meehan B, Micallef J, Lhotak V, May L, Guha A, Rak J. 2008 Intercellular transfer of the oncogenic receptor EGFRvIII by microvesicles derived from tumour cells. Nat. Cell Biol. 10, 619-624. (doi:10.1038/ncb1725)
65. Al-Nedawi K, Meehan B, Rak J. 2009 Microvesicles: messengers and mediators of tumor progression. Cell Cycle 8, 2014-2018. (doi:10.4161/cc.8.13.8988)
66. Al-Nedawi K, Meehan B, Kerbel RS, Allison AC, Rak J. 2009 Endothelial expression of autocrine VEGF upon the uptake of tumor-derived microvesicles containing oncogenic EGFR. Proc. Natl Acad. Sci. USA 106, 3794-3799. (doi:10.1073/pnas.0804543106)
67. Camussi G, Deregibus MC, Bruno S, Cantaluppi V, Biancone L. 2010 Exosomes/microvesicles as a mechanism of cell-to-cell communication. Kidney Int. 78, 838-848. (doi:10.1038/ki.2010.278)
68. Lenassi M, Cagney G, Liao M, Vaupotic T, Bartholomeeusen K, Cheng Y, Krogan NJ, Plemenitas A, Peterlin BM. 2010 HIV Nef is secreted in exosomes and triggers apoptosis in bystander CD4{thorn} T cells. Traffic 11, 110-122. (doi:10.1111/j. 1600-0854.2009.01006.x)
69. Izquierdo-Useros N et al. 2009 Capture and transfer of HIV-1 particles by mature dendritic cells converges with the exosome-dissemination pathway. Blood 113, 2732-2741. (doi:10.1182/ blood-2008-05-158642)
70. Izquierdo-Useros N, Naranjo-Gómez M, Erkizia I, Puertas MC, Borràs FE, Blanco J, Martinez-Picado J. 2010 HIV and mature dendritic cells: Trojan exosomes riding the Trojan horse? PLoS Pathog. 6, e1000740. (doi:10.1371/journal.ppat.1000740)
71. Skog J et al. 2008 Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat. Cell Biol. 10, 1470-1476. (doi:10.1038/ncb1800)
72. Janowska-Wieczorek A, Wysoczynski M, Kijowski J, Marquez-Curtis L, Machalinski B, Ratajczak J, Ratajczak MZ. 2005 Microvesicles derived from activated platelets induce metastasis and angiogenesis in lung cancer. Int. J. Cancer 113, 752-760. (doi:10.1002/ijc.20657)
73. Genneback N, Hellman U, Malm L, Larsson G, Ronquist G, Waldenstrom A, Morner S. 2013 Growth factor stimulation of cardiomyocytes induces changes in the transcriptional contents of secreted exosomes. J. Extracellular Ves. 2, 20167.
74. Yuan XL et al. 2010 Elevated expression of Foxp3 in tumor-infiltrating Treg cells suppresses T-cell proliferation and contributes to gastric cancer progression in a COX-2-dependent manner. Clin. Immunol. 134, 277-288. (doi:10.1016/j.clim.2009.10.005)
75. Cohen SM. 2010 microRNA in CNS development and neurodegradation. In Macro roles for microRNAs in the life and death of neurons (eds B de Stooper, Y Christen), pp. 69-77. Berlin, Germany: Springer.
76. Abe M, Bonini NM. 2013 MicroRNAs and neurodegeneration: role and impact. Trends Cell Biol. 23, 30-36. (doi:10.1016/j.tcb.2012.08.013)
77. Gascon E, Gao FB. 2012 Cause or effect: misregulation of microRNA pathways in neurodegeneration. Front. Neurosci. 6, 48. (doi:10. 3389/fnins.2012.00048)
78. Redell JB, Moore AN, Ward NH, Hergenroeder GW, Dash PK. 2010 Human traumatic brain injury alters plasma microRNA levels. J. Neurotrauma 27, 2147-2156. (doi:10.1089/neu.2010.1481)
79. Mathivanan S, Simpson RJ. 2009 ExoCarta: a compendium of exosomal proteins and RNA. Proteomics 9, 4997-5000. (doi:10.1002/pmic. 200900351)
80. Doring T, Gotthardt K, Stieler J, Prange R. 2010 g2-Adaptin is functioning in the late endosomal sorting pathway and interacts with ESCRT-I and-III subunits. Biochim. Biophys. Acta 1803, 1252-1264. (doi:10.1016/j.bbamcr.2010.08.001)
81. Graner MW, Alzate O, Dechkovskaia AM, Keene JD, Sampson JH, Mitchell DA, Bigner DD. 2009 Proteomic and immunologic analyses of brain tumor exosomes. FASEB J. 23, 1541-1557. (doi:10. 1096/fj.08-122184)
82. Simpson RJ et al. 2012 Vesiclepedia: a compendium for extracellular vesicles that enables continuous annotation. PLoS Biol. 10, e1001450. (doi:10.1371/ journal.pbio.1001450)
83. Mitchell PS et al. 2008 Circulating microRNAs as stable blood-based markers for cancer detection. Proc. Natl Acad. Sci. USA 105, 10 513-10 518. (doi:10.1073/pnas.0804549105)
84. Chen X, Liang H, Zhang J, Zen K, Zhang CY. 2012 Horizontal transfer of microRNAs: molecular mechanisms and clinical applications. Protein Cell 3, 28-37. (doi:10.1007/s13238-012-2003-z)
85. Duggagupta R, Jiang R, Gollub J, Getts RC, Jones KW. 2011 Impact of cellular miRNAs on circulating miRNA biomarker signatures. PLoS ONE 6, e20769. (doi:10.1371/journal.pone.0020769)
86. Zhang Y et al. 2010 Secreted monocytic miR-150 enhances targeted endothelial cell migration. Mol. Cell 39, 33-144. (doi:10.1016/j.molcel.2010.06.010)
87. Simons M, Raposo G. 2009 Exosomes: vesicular carriers for intercellular communication. Curr. Opin. Cell Biol. 21, 575-581. (doi:10.1016/j.ceb.2009.03. 007)
88. Pigati L, Yaddanapudi SC, Iyengar R, Kim DJ, Hearn SA, Danforth D, Hastings ML, Duelli DM. 2010 Selective release of microRNA species from normal and malignant mammary epithelial cells. PLoS ONE 5, e13515. (doi:10.1371/journal.pone.0013515)
89. Rabinowits G, Gercel-Taylor C, Day JM, Taylor DD, Kloecker GH. 2009 Exosomal microRNA: a diagnostic marker for lung cancer. Clin. Lung Cancer 10, 42-46. (doi:10.3816/CLC.2009.n.006)
90. Mittelbrunn M, Gutiérrez-Vázquez C, Villarroya-Beltri C, González S, Sánchez-Cabo F, González Má, Bernad A, Sánchez-Madrid F. 2011 Unidirectional transfer of microRNA-loaded exosomes from T cells to antigen-presenting cells. Nat. Commun. 2, 282. (doi:10.1038/ncomms1285)
91. Zhang Y, Liao JM, Zeng SX, Lu H. 2011 p53 downregulates Down syndrome-associated DYRK1A through miR-1246. EMBO Rep. 12, 811-817. (doi:10.1038/embor.2011.98)
92. El-Andaloussi S, Lee Y, Lakhal-Littleton S, Li J, Seow Y, Gardiner C, Alvarez-Erviti L, Sargent IL, Wood MJ. 2012 Exosome-mediated delivery of siRNA in vitro and in vivo. Nat. Protoc. 7, 2112-2126. (doi:10. 1038/nprot.2012.131)
93. Tetta C, Ghigo E, Silengo L, Deregibus MC, Camussi G. 2013 Extracellular vesicles as an emerging mechanism of cell-to-cell communication. Endocrine 44, 11-19. (doi:10.1007/s12020-012-9839-0)
94. Huang X et al. 2013 Characterization of human plasmaderived exosomal RNAs by deep sequencing. BMC Genomics 14, 319. (doi:10.1186/1471-2164-14-319)
95. Cheng J, Deng H, Xiao B, Zhou H, Zhou F, Shen Z, Guo J. 2012 piR-823, a novel non-coding small RNA, demonstrates in vitro and in vivo tumor suppressive activity in human gastric cancer cells. Cancer Lett. 315, 12-17. (doi:10.1016/j.canlet.2011.10.004)
96. Cheng J, Guo JM, Xiao BX, Miao Y, Jiang Z, Zhou H, Li QN. 2011 piRNA, the new non-coding RNA, is aberrantly expressed in human cancer cells. Clin. Chim. Acta 412, 1621-1625. (doi:10.1016/j.cca. 2011.05.015)
97. Kim JW, Galanzha EI, Zaharoff DA, Griffin RJ, Zharov VP. 2013 Nanotheranostics of circulating tumor cells, infections and other pathological features in vivo. Mol. Pharm. 10, 813-830. (doi:10.1021/ mp300577s)
98. Liang B et al. 2013 Characterization and proteomic analysis of ovarian cancer-derived exosomes. J. Proteomics 80C, 171-182. (doi:10.1016/j.jprot. 2012.12.029)
99. Takeshita N et al. 2013 Serum microRNA expression profile: miR-1246 as a novel diagnostic and prognostic biomarker for oesophageal squamous cell carcinoma. Br. J. Cancer 108, 644-652. (doi:10. 1038/bjc.2013.8)