Extracellular vesicles and the application of system biology and computational modeling in cardiac repair

Circulation Research

Volumn 123, Issue 2, 2018, Pages 188-204

  Garikipati, Venkata Naga Srikanth ^a   Shoja Taheri, Farnaz ^b,c   Davis, Michael E ^b,c   Kishore, Raj ^a  

^a TEMPLE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b GEORGIA INSTITUTE OF TECHNOLOGY   (United States)

^c EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Biology; Exosomes; Extracellular vesicles; Lipids; Stem cells

Indexed keywords

BIOLOGICAL MARKER; MICRORNA;

ARTICLE; BIOGENESIS; CARDIAC MUSCLE CELL; CARDIAC STEM CELL; CELL ACTIVITY; CELL COMMUNICATION; CELL FUNCTION; CELL ISOLATION; CELL THERAPY; CELL TRANSPLANTATION; COMPUTER MODEL; ENDOTHELIAL PROGENITOR CELL; ENDOTHELIUM CELL; EXOSOME; FIBROBLAST; GRAFT RECIPIENT; HEART SURGERY; HUMAN; IN VIVO STUDY; MACROPHAGE; MESENCHYMAL STROMA CELL; NONHUMAN; PERICARDIAL EFFUSION; PLASMA CELL; PLURIPOTENT STEM CELL; PRIORITY JOURNAL; STEM CELL; STEM CELL TRANSPLANTATION; ANIMAL; CARDIOVASCULAR DISEASE; CLASSIFICATION; GENETICS; PROCEDURES; SYSTEMS BIOLOGY; TRANSPLANTATION;

ANIMALS; CARDIOVASCULAR DISEASES; EXTRACELLULAR VESICLES; HUMANS; MICRORNAS; STEM CELL TRANSPLANTATION; SYSTEMS BIOLOGY;

EID: 85056554777     PISSN: 00097330     EISSN: 15244571     Source Type: Journal    
DOI: 10.1161/CIRCRESAHA.117.311215     Document Type: Article

References (167)

1. Mozaffarian D, Benjamin EJ, Go AS, et al; Writing Group Members; American Heart Association Statistics Committee; Stroke Statistics Subcommittee. Heart disease and stroke statistics-2016 update: a report from the American Heart Association. Circulation. 2016;133:e38-e360. doi: 10.1161/CIR.0000000000000350.
2. Hodgkinson CP, Bareja A, Gomez JA, Dzau VJ. Emerging concepts in paracrine mechanisms in regenerative cardiovascular medicine and biology. Circ Res. 2016;118:95-107. doi: 10.1161/CIRCRESAHA.115.305373.
3. Ibrahim AG, Cheng K, Marbán E. Exosomes as critical agents of cardiac regeneration triggered by cell therapy. Stem Cell Reports. 2014;2:606-619. doi: 10.1016/j.stemcr.2014.04.006.
4. Kishore R, Garikipati VN, Gumpert A. Tiny shuttles for information transfer: exosomes in cardiac health and disease. J Cardiovasc Transl Res. 2016;9:169-175. doi: 10.1007/s12265-016-9682-4.
5. El Andaloussi S, Mager I, Breakefield XO, Wood MJ. Extracellular vesicles: biology and emerging therapeutic opportunities. Nat Rev Drug Discov. 2013;12:347-357.
6. Sahoo S, Klychko E, Thorne T, Misener S, Schultz KM, Millay M, Ito A, Liu T, Kamide C, Agrawal H, Perlman H, Qin G, Kishore R, Losordo DW. Exosomes from human CD34(+) stem cells mediate their proangiogenic paracrine activity. Circ Res. 2011;109:724-728. doi: 10.1161/CIRCRESAHA.111.253286.
7. Sharma S, Mishra R, Bigham GE, et al. A deep proteome analysis identifies the complete secretome as the functional unit of human cardiac progenitor cells. Circ Res. 2017;120:816-834.
8. Trajkovic K, Hsu C, Chiantia S, Rajendran L, Wenzel D, Wieland F, Schwille P, Brügger B, Simons M. Ceramide triggers budding of exosome vesicles into multivesicular endosomes. Science. 2008;319:1244-1247. doi: 10.1126/science.1153124.
9. Colombo M, Moita C, van Niel G, Kowal J, Vigneron J, Benaroch P, Manel N, Moita LF, Théry 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. doi: 10.1242/jcs.128868.
10. van Niel G, Charrin S, Simoes S, Romao M, Rochin L, Saftig P, Marks MS, Rubinstein E, Raposo G. The tetraspanin CD63 regulates ESCRTindependent and -dependent endosomal sorting during melanogenesis. Dev Cell. 2011;21:708-721. doi: 10.1016/j.devcel.2011.08.019.
11. Ostrowski M, Carmo NB, Krumeich S, et al. Rab27a and Rab27b control different steps of the exosome secretion pathway. Nat Cell Biol. 2010;12:19-30. doi: 10.1038/ncb2000.
12. Baietti MF, Zhang Z, Mortier E, Melchior A, Degeest G, Geeraerts A, Ivarsson Y, Depoortere F, Coomans C, Vermeiren E, Zimmermann P, David G. Syndecan-syntenin-ALIX regulates the biogenesis of exosomes. Nat Cell Biol. 2012;14:677-685. doi: 10.1038/ncb2502.
13. Zylbersztejn K, Galli T. Vesicular traffic in cell navigation. FEBS J. 2011;278:4497-4505. doi: 10.1111/j.1742-4658.2011.08168.x.
14. Yu X, Harris SL, Levine AJ. The regulation of exosome secretion: a novel function of the p53 protein. Cancer Res. 2006;66:4795-4801. doi: 10.1158/0008-5472.CAN-05-4579.
15. Yue Y, Garikipati VNS, Verma SK, Goukassian DA, Kishore R. Interleukin-10 deficiency impairs reparative properties of bone marrow-derived endothelial progenitor cell exosomes. Tissue Eng Part A. 2017;23:1241-1250. doi: 10.1089/ten.TEA.2017.0084.
16. Hugel B, Martínez MC, Kunzelmann C, Freyssinet JM. Membrane microparticles: two sides of the coin. Physiology (Bethesda). 2005;20:22-27. doi: 10.1152/physiol.00029.2004.
17. Pasquet JM, Dachary-Prigent J, Nurden AT. Calcium influx is a determining factor of calpain activation and microparticle formation in platelets. Eur J Biochem. 1996;239:647-654.
18. Colombo M, Raposo G, Théry C. Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annu Rev Cell Dev Biol. 2014;30:255-289. doi: 10.1146/annurev-cellbio-101512-122326.
19. Greco V, Hannus M, Eaton S. Argosomes: a potential vehicle for the spread of morphogens through epithelia. Cell. 2001;106:633-645.
20. Coumans FAW, Brisson AR, Buzas EI, et al. Methodological guidelines to study extracellular vesicles. Circ Res. 2017;120:1632-1648. doi: 10.1161/CIRCRESAHA.117.309417.
21. György B, Szabó TG, Pásztói M, Pál Z, Misják P, Aradi B, László V, Pállinger E, Pap E, Kittel A, Nagy G, Falus A, Buzás EI. Membrane vesicles, current state-of-the-art: emerging role of extracellular vesicles. Cell Mol Life Sci. 2011;68:2667-2688. doi: 10.1007/s00018-011-0689-3.
22. Théry C, Amigorena S, Raposo G, Clayton A. Isolation and characterization of exosomes from cell culture supernatants and biological fluids. Curr Protoc Cell Biol. 2006;Chapter 3:Unit 3.22. doi: 10.1002/0471143030.cb0322s30.
23. Livshits MA, Livshts MA, Khomyakova E, Evtushenko EG, Lazarev VN, Kulemin NA, Semina SE, Generozov EV, Govorun VM. Isolation of exosomes by differential centrifugation: theoretical analysis of a commonly used protocol. Sci Rep. 2015;5:17319. doi: 10.1038/srep17319.
24. Kowal J, Arras G, Colombo M, Jouve M, Morath JP, Primdal-Bengtson B, Dingli F, Loew D, Tkach M, Théry C. Proteomic comparison defines novel markers to characterize heterogeneous populations of extracellular vesicle subtypes. Proc Natl Acad Sci USA. 2016;113:E968-E977. doi: 10.1073/pnas.1521230113.
25. Mateescu B, Kowal EJ, van Balkom BW, et al. Obstacles and opportunities in the functional analysis of extracellular vesicle RNA-an ISEV position paper. J Extracell Vesicles. 2017;6:1286095. doi: 10.1080/20013078.2017.1286095.
26. Yuana Y, Levels J, Grootemaat A, Sturk A, Nieuwland R. Co-isolation of extracellular vesicles and high-density lipoproteins using density gradient ultracentrifugation. J Extracell Vesicles. 2014;3. doi: 10.3402/jev.v3.23262.
27. Boing AN, van der Pol E, Grootemaat AE, Coumans FA, Sturk A, Nieuwland R. Single-step isolation of extracellular vesicles by size-exclusion chromatography. J Extracell Vesicles. 2014;3.
28. Baranyai T, Herczeg K, Onódi Z, et al. Isolation of exosomes from blood plasma: qualitative and quantitative comparison of ultracentrifugation and size exclusion chromatography methods. PLoS One. 2015;10:e0145686. doi: 10.1371/journal.pone.0145686.
29. Welton JL, Webber JP, Botos LA, Jones M, Clayton A. Ready-made chromatography columns for extracellular vesicle isolation from plasma. J Extracell Vesicles. 2015;4:27269.
30. Scientific program 2012 ISEV meeting Wednesday 18th april. J Extracell Vesicles. 2012;1:18182.
31. Liang LG, Kong MQ, Zhou S, Sheng YF, Wang P, Yu T, Inci F, Kuo WP, Li LJ, Demirci U, Wang S. An integrated double-filtration microfluidic device for isolation, enrichment and quantification of urinary extracellular vesicles for detection of bladder cancer. Sci Rep. 2017;7:46224. doi: 10.1038/srep46224.
32. Sluijter JPG, Davidson SM, Boulanger CM, et al. Extracellular vesicles in diagnostics and therapy of the ischaemic heart: position paper from the Working Group on Cellular Biology of the Heart of the European Society of Cardiology. Cardiovasc Res. 2018;114:19-34. doi: 10.1093/cvr/cvx211.
33. Van Deun J, Mestdagh P, Agostinis P, et al; EV-TRACK Consortium. EV-TRACK: transparent reporting and centralizing knowledge in extracellular vesicle research. Nat Methods. 2017;14:228-232. doi: 10.1038/nmeth.4185.
34. Lötvall J, Hill AF, Hochberg F, Buzás EI, Di Vizio D, Gardiner C, Gho YS, Kurochkin IV, Mathivanan S, Quesenberry P, Sahoo S, Tahara H, Wauben MH, Witwer KW, Théry 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.
35. Yoshioka Y, Konishi Y, Kosaka N, Katsuda T, Kato T, Ochiya T. Comparative marker analysis of extracellular vesicles in different human cancer types. J Extracell Vesicles. 2013;2. doi: 10.3402/jev.v2i0.20424.
36. Belov L, Matic KJ, Hallal S, Best OG, Mulligan SP, Christopherson RI. Extensive surface protein profiles of extracellular vesicles from cancer cells may provide diagnostic signatures from blood samples. J Extracell Vesicles. 2016;5:25355.
37. Muntasell A, Berger AC, Roche PA. T cell-induced secretion of MHC class II-peptide complexes on B cell exosomes. EMBO J. 2007;26:4263-4272. doi: 10.1038/sj.emboj.7601842.
38. Quah BJ, O'Neill HC. The immunogenicity of dendritic cellderived exosomes. Blood Cells Mol Dis. 2005;35:94-110. doi: 10.1016/j.bcmd.2005.05.002.
39. Guduric-Fuchs J, O'Connor A, Camp B, O'Neill CL, Medina RJ, Simpson DA. Selective extracellular vesicle-mediated export of an overlapping set of microRNAs from multiple cell types. BMC Genomics. 2012;13:357. doi: 10.1186/1471-2164-13-357.
40. Squadrito ML, Baer C, Burdet F, Maderna C, Gilfillan GD, 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. doi: 10.1016/j.celrep.2014.07.035.
41. Kosaka N, Iguchi H, Hagiwara K, Yoshioka Y, Takeshita F, Ochiya T. Neutral sphingomyelinase 2 (nSMase2)-dependent exosomal transfer of angiogenic microRNAs regulate cancer cell metastasis. J Biol Chem. 2013;288:10849-10859. doi: 10.1074/jbc.M112.446831.
42. 2B 1 controls the sorting of miRNAs into exosomes through binding to specific motifs. Nat Commun. 2013;4:2980. doi: 10.1038/ncomms3980.
43. Lee WH, Chen WY, Shao NY, Xiao D, Qin X, Baker N, Bae HR, Wei TT, Wang Y, Shukla P, Wu H, Kodo K, Ong SG, Wu JC. Comparison of noncoding RNAs in exosomes and functional efficacy of human embryonic stem cell-versus induced pluripotent stem cell-derived cardiomyocytes. Stem Cells. 2017;35:2138-2149.
44. Cambier L, de Couto G, Ibrahim A, Echavez AK, Valle J, Liu W, Kreke M, Smith RR, Marbán L, Marbán E. Y RNA fragment in extracellular vesicles confers cardioprotection via modulation of IL-10 expression and secretion. EMBO Mol Med. 2017;9:337-352. doi: 10.15252/emmm.201606924.
45. Brisson AR, Tan S, Linares R, Gounou C, Arraud N. Extracellular vesicles from activated platelets: a semiquantitative cryo-electron microscopy and immuno-gold labeling study. Platelets. 2017;28:263-271. doi: 10.1080/09537104.2016.1268255.
46. Arraud N, Linares R, Tan S, Gounou C, Pasquet JM, Mornet S, Brisson AR. Extracellular vesicles from blood plasma: determination of their morphology, size, phenotype and concentration. J Thromb Haemost. 2014;12:614-627. doi: 10.1111/jth.12554.
47. Yuana Y, Oosterkamp TH, Bahatyrova S, Ashcroft B, Garcia Rodriguez P, Bertina RM, Osanto S. Atomic force microscopy: a novel approach to the detection of nanosized blood microparticles. J Thromb Haemost. 2010;8:315-323. doi: 10.1111/j.1538-7836.2009.03654.x.
48. Arraud N, Gounou C, Turpin D, Brisson AR. Fluorescence triggering: a general strategy for enumerating and phenotyping extracellular vesicles by flow cytometry. Cytometry A. 2016;89:184-195. doi: 10.1002/cyto.a.22669.
49. Boulanger CM, Loyer X, Rautou PE, Amabile N. Extracellular vesicles in coronary artery disease. Nat Rev Cardiol. 2017;14:259-272. doi: 10.1038/nrcardio.2017.7.
50. Groot Kormelink T, Arkesteijn GJ, Nauwelaers FA, van den Engh G, Nolte-'t Hoen EN, Wauben MH. Prerequisites for the analysis and sorting of extracellular vesicle subpopulations by high-resolution flow cytometry. Cytometry A. 2016;89:135-147. doi: 10.1002/cyto.a.22644.
51. Gardiner C, Ferreira YJ, Dragovic RA, Redman CW, Sargent IL. Extracellular vesicle sizing and enumeration by nanoparticle tracking analysis. J Extracell Vesicles. 2013;2. doi: 10.3402/jev.v2i0.19671.
52. Filipe V, Hawe A, Jiskoot W. Critical evaluation of Nanoparticle Tracking Analysis (NTA) by NanoSight for the measurement of nanoparticles and protein aggregates. Pharm Res. 2010;27:796-810. doi: 10.1007/s11095-010-0073-2.
53. Osteikoetxea X, Balogh A, Szabó-Taylor K, Németh A, Szabó TG, Pálóczi K, Sódar B, Kittel Á, György B, Pállinger É, Matkó J, Buzás EI. Improved characterization of EV preparations based on protein to lipid ratio and lipid properties. PLoS One. 2015;10:e0121184. doi: 10.1371/journal.pone.0121184.
54. Webber J, Clayton A. How pure are your vesicles? J Extracell Vesicles. 2013;2. doi: 10.3402/jev.v2i0.19861.
55. Sódar BW, Kittel Á, Pálóczi K, et al. Low-density lipoprotein mimics blood plasma-derived exosomes and microvesicles during isolation and detection. Sci Rep. 2016;6:24316. doi: 10.1038/srep24316.
56. van der Pol E, Coumans FA, Grootemaat AE, Gardiner C, Sargent IL, Harrison P, Sturk A, van Leeuwen TG, Nieuwland R. Particle size distribution of exosomes and microvesicles determined by transmission electron microscopy, flow cytometry, nanoparticle tracking analysis, and resistive pulse sensing. J Thromb Haemost. 2014;12:1182-1192. doi: 10.1111/jth.12602.
57. Coumans FA, van der Pol E, Böing AN, Hajji N, Sturk G, van Leeuwen TG, Nieuwland R. Reproducible extracellular vesicle size and concentration determination with tunable resistive pulse sensing. J Extracell Vesicles. 2014;3:25922.
58. Im H, Shao H, Park YI, Peterson VM, Castro CM, Weissleder R, Lee H. Label-free detection and molecular profiling of exosomes with a nano-plasmonic sensor. Nat Biotechnol. 2014;32:490-495. doi: 10.1038/nbt.2886.
59. Heusermann W, Hean J, Trojer D, Steib E, von Bueren S, Graff-Meyer A, Genoud C, Martin K, Pizzato N, Voshol J, Morrissey DV, Andaloussi SE, Wood MJ, Meisner-Kober NC. Exosomes surf on filopodia to enter cells at endocytic hot spots, traffic within endosomes, and are targeted to the ER. J Cell Biol. 2016;213:173-184. doi: 10.1083/jcb.201506084.
60. Vicencio JM, Yellon DM, Sivaraman V, Das D, Boi-Doku C, Arjun S, Zheng Y, Riquelme JA, Kearney J, Sharma V, Multhoff G, Hall AR, Davidson SM. Plasma exosomes protect the myocardium from ischemia-reperfusion injury. J Am Coll Cardiol. 2015;65:1525-1536. doi: 10.1016/j.jacc.2015.02.026.
61. Gupta S, Knowlton AA. HSP60 trafficking in adult cardiac myocytes: role of the exosomal pathway. Am J Physiol Heart Circ Physiol. 2007;292:H3052-H3056. doi: 10.1152/ajpheart.01355.2006.
62. Yu X, Deng L, Wang D, Li N, Chen X, Cheng X, Yuan J, Gao X, Liao M, Wang M, Liao Y. Mechanism of TNF-α autocrine effects in hypoxic cardiomyocytes: initiated by hypoxia inducible factor 1α, presented by exosomes. J Mol Cell Cardiol. 2012;53:848-857. doi: 10.1016/j.yjmcc.2012.10.002.
63. Pironti G, Strachan RT, Abraham D, Mon-Wei Yu S, Chen M, Chen W, Hanada K, Mao L, Watson LJ, Rockman HA. Circulating exosomes induced by cardiac pressure overload contain functional angiotensin II type 1 receptors. Circulation. 2015;131:2120-2130. doi: 10.1161/CIRCULATIONAHA.115.015687.
64. Garcia NA, Moncayo-Arlandi J, Sepulveda P, Diez-Juan A. Cardiomyocyte exosomes regulate glycolytic flux in endothelium by direct transfer of GLUT transporters and glycolytic enzymes. Cardiovasc Res. 2016;109:397-408. doi: 10.1093/cvr/cvv260.
65. Garcia NA, Ontoria-Oviedo I, González-King H, Diez-Juan A, Sepúlveda P. Glucose starvation in cardiomyocytes enhances exosome secretion and promotes angiogenesis in endothelial cells. PLoS One. 2015;10:e0138849. doi: 10.1371/journal.pone.0138849.
66. Wang X, Huang W, Liu G, Cai W, Millard RW, Wang Y, Chang J, Peng T, Fan GC. Cardiomyocytes mediate anti-angiogenesis in type 2 diabetic rats through the exosomal transfer of miR-320 into endothelial cells. J Mol Cell Cardiol. 2014;74:139-150. doi: 10.1016/j.yjmcc.2014.05.001.
67. Lyu L, Wang H, Li B, Qin Q, Qi L, Nagarkatti M, Nagarkatti P, Janicki JS, Wang XL, Cui T. A critical role of cardiac fibroblast-derived exosomes in activating renin angiotensin system in cardiomyocytes. J Mol Cell Cardiol. 2015;89:268-279. doi: 10.1016/j.yjmcc.2015.10.022.
68. Bang C, Batkai S, Dangwal S, et al. Cardiac fibroblast-derived microRNA passenger strand-enriched exosomes mediate cardiomyocyte hypertrophy. J Clin Invest. 2014;124:2136-2146. doi: 10.1172/JCI70577.
69. Wang C, Zhang C, Liu L, A X, Chen B, Li Y, Du J. Macrophagederived mir-155-containing exosomes suppress fibroblast proliferation and promote fibroblast inflammation during cardiac injury. Mol Ther. 2017;25:192-204. doi: 10.1016/j.ymthe.2016.09.001.
70. van Balkom BW, de Jong OG, Smits M, Brummelman J, den Ouden K, de Bree PM, van Eijndhoven MA, Pegtel DM, Stoorvogel W, Würdinger T, Verhaar MC. Endothelial cells require miR-214 to secrete exosomes that suppress senescence and induce angiogenesis in human and mouse endothelial cells. Blood. 2013;121:3997-4006, S1-S15. doi: 10.1182/blood-2013-02-478925.
71. Halkein J, Tabruyn SP, Ricke-Hoch M, Haghikia A, Nguyen NQ, Scherr M, Castermans K, Malvaux L, Lambert V, Thiry M, Sliwa K, Noel A, Martial JA, Hilfiker-Kleiner D, Struman I. MicroRNA-146a is a therapeutic target and biomarker for peripartum cardiomyopathy. J Clin Invest. 2013;123:2143-2154. doi: 10.1172/JCI64365.
72. Woodcock EA, Matkovich SJ. Cardiomyocytes structure, function and associated pathologies. Int J Biochem Cell Biol. 2005;37:1746-1751. doi: 10.1016/j.biocel.2005.04.011.
73. Davidson SM, Riquelme JA, Takov K, Vicencio JM, Boi-Doku C, Khoo V, Doreth C, Radenkovic D, Lavandero S, Yellon DM. Cardioprotection mediated by exosomes is impaired in the setting of type II diabetes but can be rescued by the use of non-diabetic exosomes in vitro. J Cell Mol Med. 2018;22:141-151. doi: 10.1111/jcmm.13302.
74. Watanabe M, Kawaguchi S, Nakahara H, Hachimaru T. The roles of natriuretic peptides in pericardial fluid in patients with heart failure. Clin Cardiol. 2009;32:159-163. doi: 10.1002/clc.20306.
75. Beltrami C, Besnier M, Shantikumar S, Shearn AI, Rajakaruna C, Laftah A, Sessa F, Spinetti G, Petretto E, Angelini GD, Emanueli C. Human pericardial fluid contains exosomes enriched with cardiovascular-expressed microRNAs and promotes therapeutic angiogenesis. Mol Ther. 2017;25:679-693. doi: 10.1016/j.ymthe.2016.12.022.
76. Foglio E, Puddighinu G, Fasanaro P, et al. Exosomal clusterin, identified in the pericardial fluid, improves myocardial performance following MI through epicardial activation, enhanced arteriogenesis and reduced apoptosis. Int J Cardiol. 2015;197:333-347. doi: 10.1016/j.ijcard.2015.06.008.
77. Garikipati VN, Krishnamurthy P, Verma SK, Khan M, Abramova T, Mackie AR, Qin G, Benedict C, Nickoloff E, Johnson J, Gao E, Losordo DW, Houser SR, Koch WJ, Kishore R. Negative regulation of miR-375 by interleukin-10 enhances bone marrow-derived progenitor cell-mediated myocardial repair and function after myocardial infarction. Stem Cells. 2015;33:3519-3529. doi: 10.1002/stem.2121.
78. Krishnamurthy P, Thal M, Verma S, Hoxha E, Lambers E, Ramirez V, Qin G, Losordo D, Kishore R. Interleukin-10 deficiency impairs bone marrow-derived endothelial progenitor cell survival and function in ischemic myocardium. Circ Res. 2011;109:1280-1289. doi: 10.1161/CIRCRESAHA.111.248369.
79. + cells deficient in microRNA-377. J Am Coll Cardiol. 2015;66:2214-2226. doi: 10.1016/j.jacc.2015.09.009.
80. Rajasingh J, Lambers E, Hamada H, Bord E, Thorne T, Goukassian I, Krishnamurthy P, Rosen KM, Ahluwalia D, Zhu Y, Qin G, Losordo DW, Kishore R. Cell-free embryonic stem cell extract-mediated derivation of multipotent stem cells from NIH3T3 fibroblasts for functional and anatomical ischemic tissue repair. Circ Res. 2008;102:e107-e117. doi: 10.1161/CIRCRESAHA.108.176115.
81. Rajasingh J, Bord E, Hamada H, Lambers E, Qin G, Losordo DW, Kishore R. STAT3-dependent mouse embryonic stem cell differentiation into cardiomyocytes: analysis of molecular signaling and therapeutic efficacy of cardiomyocyte precommitted mES transplantation in a mouse model of myocardial infarction. Circ Res. 2007;101:910-918. doi: 10.1161/CIRCRESAHA.107.156786.
82. Cheng K, Li TS, Malliaras K, Davis DR, Zhang Y, Marbán E. Magnetic targeting enhances engraftment and functional benefit of iron-labeled cardiosphere-derived cells in myocardial infarction. Circ Res. 2010;106:1570-1581. doi: 10.1161/CIRCRESAHA.109.212589.
83. Mohsin S, Khan M, Toko H, et al. Human cardiac progenitor cells engineered with Pim-I kinase enhance myocardial repair. J Am Coll Cardiol. 2012;60:1278-1287. doi: 10.1016/j.jacc.2012.04.047.
84. Williams AR, Suncion VY, McCall F, Guerra D, Mather J, Zambrano JP, Heldman AW, Hare JM. Durable scar size reduction due to allogeneic mesenchymal stem cell therapy regulates whole-chamber remodeling. J Am Heart Assoc. 2013;2:e000140. doi: 10.1161/JAHA.113.000140.
85. Williams AR, Hatzistergos KE, Addicott B, McCall F, Carvalho D, Suncion V, Morales AR, Da Silva J, Sussman MA, Heldman AW, Hare JM. Enhanced effect of combining human cardiac stem cells and bone marrow mesenchymal stem cells to reduce infarct size and to restore cardiac function after myocardial infarction. Circulation. 2013;127:213-223. doi: 10.1161/CIRCULATIONAHA.112.131110.
86. Hare JM, Fishman JE, Gerstenblith G, et al. Comparison of allogeneic vs autologous bone marrow-derived mesenchymal stem cells delivered by transendocardial injection in patients with ischemic cardiomyopathy: the POSEIDON randomized trial. JAMA. 2012;308:2369-2379. doi: 10.1001/jama.2012.25321.
87. Bolli R, Chugh AR, D'Amario D, et al. Cardiac stem cells in patients with ischaemic cardiomyopathy (SCIPIO): initial results of a randomised phase 1 trial. Lancet. 2011;378:1847-1857. doi: 10.1016/S0140-6736(11)61590-0.
88. Makkar RR, Smith RR, Cheng K, Malliaras K, Thomson LE, Berman D, Czer LS, Marbán L, Mendizabal A, Johnston PV, Russell SD, Schuleri KH, Lardo AC, Gerstenblith G, Marbán E. Intracoronary cardiosphere-derived cells for heart regeneration after myocardial infarction (CADUCEUS): a prospective, randomised phase 1 trial. Lancet. 2012;379:895-904. doi: 10.1016/S0140-6736(12)60195-0.
89. Smits PC, van Geuns RJ, Poldermans D, Bountioukos M, Onderwater EE, Lee CH, Maat AP, Serruys PW. Catheter-based intramyocardial injection of autologous skeletal myoblasts as a primary treatment of ischemic heart failure: clinical experience with six-month follow-up. J Am Coll Cardiol. 2003;42:2063-2069.
90. + cells in patients with left ventricular dysfunction post STEMI. Circ Res. 2017;120:324-331. doi: 10.1161/CIRCRESAHA.115.308165.
91. + stem cell transplantation in nonischemic dilated cardiomyopathy patients: 5-year follow-up. Circ Res. 2013;112:165-173. doi: 10.1161/CIRCRESAHA.112.276519.
92. Khan M, Nickoloff E, Abramova T, et al. Embryonic stem cell-derived exosomes promote endogenous repair mechanisms and enhance cardiac function following myocardial infarction. Circ Res. 2015;117:52-64. doi: 10.1161/CIRCRESAHA.117.305990.
93. Agarwal U, George A, Bhutani S, Ghosh-Choudhary S, Maxwell JT, Brown ME, Mehta Y, Platt MO, Liang Y, Sahoo S, Davis ME. Experimental, systems, and computational approaches to understanding the microRNA-mediated reparative otential of cardiac progenitor cellderived exosomes from pediatric patients. Circ Res. 2017;120:701-712. doi: 10.1161/CIRCRESAHA.116.309935.
94. + cells preserve cardiac function after acute myocardial infarction. Circ Res. 2012;111:312-321. doi: 10.1161/CIRCRESAHA.112.266015.
95. + stem cell exosomes in the repair of ischemic hindlimb. Circ Res. 2017;120:1466-1476. doi: 10.1161/CIRCRESAHA.116.310557.
96. Wang Y, Zhang L, Li Y, Chen L, Wang X, Guo W, Zhang X, Qin G, He SH, Zimmerman A, Liu Y, Kim IM, Weintraub NL, Tang Y. Exosomes/microvesicles from induced pluripotent stem cells deliver cardioprotective miRNAs and prevent cardiomyocyte apoptosis in the ischemic myocardium. Int J Cardiol. 2015;192:61-69. doi: 10.1016/j.ijcard.2015.05.020.
97. Yu B, Kim HW, Gong M, Wang J, Millard RW, Wang Y, Ashraf M, Xu M. Exosomes secreted from GATA-4 overexpressing mesenchymal stem cells serve as a reservoir of anti-apoptotic microRNAs for cardioprotection. Int J Cardiol. 2015;182:349-360. doi: 10.1016/j.ijcard. 2014.12.043.
98. 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 (Berl). 2014;92:387-397. doi: 10.1007/s00109-013-1110-5.
99. Feng Y, Huang W, Wani M, Yu X, Ashraf M. Ischemic preconditioning potentiates the protective effect of stem cells through secretion of exosomes by targeting Mecp2 via miR-22. PLoS One. 2014;9:e88685. doi: 10.1371/journal.pone.0088685.
100. Zhao Y, Sun X, Cao W, Ma J, Sun L, Qian H, Zhu W, Xu W. Exosomes derived from human umbilical cord mesenchymal stem cells relieve acute myocardial ischemic injury. Stem Cells Int. 2015;2015:761643. doi: 10.1155/2015/761643.
101. Vrijsen KR, Maring JA, Chamuleau SA, Verhage V, Mol EA, Deddens JC, Metz CH, Lodder K, van Eeuwijk EC, van Dommelen SM, Doevendans PA, Smits AM, Goumans MJ, Sluijter JP. Exosomes from cardiomyocyte progenitor cells and mesenchymal stem cells stimulate angiogenesis via EMMPRIN. Adv Healthc Mater. 2016;5:2555-2565. doi: 10.1002/adhm.201600308.
102. de Couto G, Gallet R, Cambier L, Jaghatspanyan E, Makkar N, Dawkins JF, Berman BP, Marbán E. Exosomal microRNA transfer into macrophages mediates cellular postconditioning. Circulation. 2017;136:200-214. doi: 10.1161/CIRCULATIONAHA.116.024590.
103. Tseliou E, Fouad J, Reich H, Slipczuk L, de Couto G, Aminzadeh M, Middleton R, Valle J, Weixin L, Marbán E. Fibroblasts rendered antifibrotic, antiapoptotic, and angiogenic by priming with cardiosphere-derived extracellular membrane vesicles. J Am Coll Cardiol. 2015;66:599-611. doi: 10.1016/j.jacc.2015.05.068.
104. Yoshida Y, Yamanaka S. Induced pluripotent stem cells 10 years later: for cardiac applications. Circ Res. 2017;120:1958-1968. doi: 10.1161/CIRCRESAHA.117.311080.
105. Bobis-Wozowicz S, Kmiotek K, Sekula M, Kedracka-Krok S, Kamycka E, Adamiak M, Jankowska U, Madetko-Talowska A, Sarna M, Bik-Multanowski M, Kolcz J, Boruczkowski D, Madeja Z, Dawn B, Zuba-Surma EK. Human induced pluripotent stem cell-derived microvesicles transmit RNAs and proteins to recipient mature heart cells modulating cell fate and behavior. Stem Cells. 2015;33:2748-2761. doi: 10.1002/stem.2078.
106. Adamiak M, Cheng G, Bobis-Wozowicz S, et al. Induced pluripotent stem cell (iPSC)-derived extracellular vesicles are safer and more effective for cardiac repair than iPSCs. Circ Res. 2018;122:296-309. doi: 10.1161/CIRCRESAHA.117.311769.
107. Garikipati VNS, Verma SK, Jolardarashi D, et al. Therapeutic inhibition of miR-375 attenuates post-myocardial infarction inflammatory response and left ventricular dysfunction via PDK-1-AKT signalling axis. Cardiovasc Res. 2017;113:938-949. doi: 10.1093/cvr/cvx052.
108. Matsushita K, Dzau VJ. Mesenchymal stem cells in obesity: insights for translational applications. Lab Invest. 2017;97:1158-1166. doi: 10.1038/labinvest.2017.42.
109. Gnecchi M, He H, Noiseux N, Liang OD, Zhang L, Morello F, Mu H, Melo LG, Pratt RE, Ingwall JS, Dzau VJ. Evidence supporting paracrine hypothesis for Akt-modified mesenchymal stem cell-mediated cardiac protection and functional improvement. FASEB J. 2006;20:661-669. doi: 10.1096/fj.05-5211com.
110. Heldman AW, DiFede DL, Fishman JE, et al. Transendocardial mesenchymal stem cells and mononuclear bone marrow cells for ischemic cardiomyopathy: the TAC-HFT randomized trial. JAMA. 2014;311:62-73. doi: 10.1001/jama.2013.282909.
111. Zhang Z, Yang J, Yan W, Li Y, Shen Z, Asahara T. Pretreatment of cardiac stem cells with exosomes derived from mesenchymal stem cells enhances myocardial repair. J Am Heart Assoc. 2016;5:e002856.
112. Gonzalez-King H, García NA, Ontoria-Oviedo I, Ciria M, Montero JA, Sepïlveda P. Hypoxia inducible factor-1α potentiates jagged 1-mediated angiogenesis by mesenchymal stem cell-derived exosomes. Stem Cells. 2017;35:1747-1759. doi: 10.1002/stem.2618.
113. Wang X, Gu H, Qin D, Yang L, Huang W, Essandoh K, Wang Y, Caldwell CC, Peng T, Zingarelli B, Fan GC. Exosomal miR-223 contributes to mesenchymal stem cellz-elicited cardioprotection in polymicrobial sepsis. Sci Rep. 2015;5:13721. doi: 10.1038/srep13721.
114. Luo L, Tang J, Nishi K, Yan C, Dinh PU, Cores J, Kudo T, Zhang J, Li TS, Cheng K. Fabrication of synthetic mesenchymal stem cells for the treatment of acute myocardial infarction in mice. Circ Res. 2017;120:1768-1775. doi: 10.1161/CIRCRESAHA.116.310374.
115. Gallet R, de Couto G, Simsolo E, Valle J, Sun B, Liu W, Tseliou E, Zile MR, Marbán E. Cardiosphere-derived cells reverse heart failure with preserved ejection fraction (HFpEF) in rats by decreasing fibrosis and inflammation. JACC Basic Transl Sci. 2016;1:14-28. doi: 10.1016/j.jacbts.2016.01.003.
116. Mohsin S, Khan M, Nguyen J, Alkatib M, Siddiqi S, Hariharan N, Wallach K, Monsanto M, Gude N, Dembitsky W, Sussman MA. Rejuvenation of human cardiac progenitor cells with Pim-1 kinase. Circ Res. 2013;113:1169-1179. doi: 10.1161/CIRCRESAHA.113.302302.
117. Barile L, Lionetti V, Cervio E, Matteucci M, Gherghiceanu M, Popescu LM, 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. doi: 10.1093/cvr/cvu167.
118. Gallet R, Dawkins J, Valle J, Simsolo E, de Couto G, Middleton R, Tseliou E, Luthringer D, Kreke M, Smith RR, Marbán L, Ghaleh B, Marbán E. Exosomes secreted by cardiosphere-derived cells reduce scarring, attenuate adverse remodelling, and improve function in acute and chronic porcine myocardial infarction. Eur Heart J. 2017;38:201-211. doi: 10.1093/eurheartj/ehw240.
119. Vrijsen KR, Sluijter JP, Schuchardt MW, van Balkom BW, Noort WA, Chamuleau SA, Doevendans PA. Cardiomyocyte progenitor cell-derived exosomes stimulate migration of endothelial cells. J Cell Mol Med. 2010;14:1064-1070. doi: 10.1111/j.1582-4934.2010.01081.x.
120. Chen L, Wang Y, Pan Y, Zhang L, Shen C, Qin G, Ashraf M, Weintraub N, Ma G, Tang Y. Cardiac progenitor-derived exosomes protect ischemic myocardium from acute ischemia/reperfusion injury. Biochem Biophys Res Commun. 2013;431:566-571. doi: 10.1016/j.bbrc.2013.01.015.
121. Gray WD, French KM, Ghosh-Choudhary S, Maxwell JT, Brown ME, Platt MO, Searles CD, Davis ME. Identification of therapeutic covariant microRNA clusters in hypoxia-treated cardiac progenitor cell exosomes using systems biology. Circ Res. 2015;116:255-263. doi: 10.1161/CIRCRESAHA.116.304360.
122. Lawson C, Vicencio JM, Yellon DM, Davidson SM. Microvesicles and exosomes: new players in metabolic and cardiovascular disease. J Endocrinol. 2016;228:R57-R71. doi: 10.1530/JOE-15-0201.
123. Lener T, Gimona M, Aigner L, et al. Applying extracellular vesicles based therapeutics in clinical trials-an ISEV position paper. J Extracell Vesicles. 2015;4:30087.
124. Chevillet JR, Kang Q, Ruf IK, et al. Quantitative and stoichiometric analysis of the microRNA content of exosomes. Proc Natl Acad Sci USA. 2014;111:14888-14893. doi: 10.1073/pnas.1408301111.
125. Lässer C, Alikhani VS, Ekström K, Eldh M, Paredes PT, Bossios A, Sjöstrand M, Gabrielsson S, Lötvall J, Valadi H. Human saliva, plasma and breast milk exosomes contain RNA: uptake by macrophages. J Transl Med. 2011;9:9. doi: 10.1186/1479-5876-9-9.
126. Morelli AE, Larregina AT, Shufesky WJ, Sullivan ML, Stolz DB, Papworth GD, Zahorchak AF, Logar AJ, Wang Z, Watkins SC, Falo LD Jr, Thomson AW. Endocytosis, intracellular sorting, and processing of exosomes by dendritic cells. Blood. 2004;104:3257-3266. doi: 10.1182/blood-2004-03-0824.
127. Théry C, Regnault A, Garin J, Wolfers J, Zitvogel L, Ricciardi-Castagnoli P, Raposo G, Amigorena S. Molecular characterization of dendritic cellderived exosomes. Selective accumulation of the heat shock protein hsc73. J Cell Biol. 1999;147:599-610.
128. Barrès C, Blanc L, Bette-Bobillo P, André S, Mamoun R, Gabius HJ, Vidal M. Galectin-5 is bound onto the surface of rat reticulocyte exosomes and modulates vesicle uptake by macrophages. Blood. 2010;115:696-705. doi: 10.1182/blood-2009-07-231449.
129. Waldenström A, Ronquist G. Role of exosomes in myocardial remodeling. Circ Res. 2014;114:315-324. doi: 10.1161/CIRCRESAHA.114.300584.
130. Escola JM, Kleijmeer MJ, Stoorvogel W, Griffith JM, Yoshie O, Geuze HJ. Selective enrichment of tetraspan proteins on the internal vesicles of multivesicular endosomes and on exosomes secreted by human B-lymphocytes. J Biol Chem. 1998;273:20121-20127.
131. Chaput N, Taïeb J, Schartz N, Flament C, Novault S, André F, Zitvogel L. The potential of exosomes in immunotherapy of cancer. Blood Cells Mol Dis. 2005;35:111-115. doi: 10.1016/j.bcmd.2005.05.009.
132. Bard MP, Hegmans JP, Hemmes A, Luider TM, Willemsen R, Severijnen LA, van Meerbeeck JP, Burgers SA, Hoogsteden HC, Lambrecht BN. Proteomic analysis of exosomes isolated from human malignant pleural effusions. Am J Respir Cell Mol Biol. 2004;31:114-121. doi: 10.1165/rcmb.2003-0238OC.
133. Emanueli C, Shearn AI, Angelini GD, Sahoo S. Exosomes and exosomal miRNAs in cardiovascular protection and repair. Vascul Pharmacol. 2015;71:24-30. doi: 10.1016/j.vph.2015.02.008.
134. Hoshino A, Costa-Silva B, Shen TL, et al. Tumour exosome integrins determine organotropic metastasis. Nature. 2015;527:329-335. doi: 10.1038/nature15756.
135. Desgrosellier JS, Cheresh DA. Integrins in cancer: biological implications and therapeutic opportunities. Nat Rev Cancer. 2010;10:9-22. doi: 10.1038/nrc2748.
136. Liu H, Gao W, Yuan J, Wu C, Yao K, Zhang L, Ma L, Zhu J, Zou Y, Ge J. Exosomes derived from dendritic cells improve cardiac function via activation of CD4(+) T lymphocytes after myocardial infarction. J Mol Cell Cardiol. 2016;91:123-133. doi: 10.1016/j.yjmcc.2015.12.028.
137. Soares AR, Martins-Marques T, Ribeiro-Rodrigues T, Ferreira JV, Catarino S, Pinho MJ, Zuzarte M, Isabel Anjo S, Manadas B, P G Sluijter J, Pereira P, Girao H. Gap junctional protein Cx43 is involved in the communication between extracellular vesicles and mammalian cells. Sci Rep. 2015;5:13243. doi: 10.1038/srep13243.
138. Loyer X, Vion AC, Tedgui A, Boulanger CM. Microvesicles as cell-cell messengers in cardiovascular diseases. Circ Res. 2014;114:345-353. doi: 10.1161/CIRCRESAHA.113.300858.
139. Boulanger CM, Leroyer AS, Amabile N, Tedgui A. [Circulating endothelial microparticles: a new marker of vascular injury]. Ann Cardiol Angeiol (Paris). 2008;57:149-154. doi: 10.1016/j.ancard.2008.02.016.
140. Benameur T, Soleti R, Porro C, Andriantsitohaina R, Martínez MC. Microparticles carrying Sonic hedgehog favor neovascularization through the activation of nitric oxide pathway in mice. PLoS One. 2010;5:e12688. doi: 10.1371/journal.pone.0012688.
141. Agouni A, Mostefai HA, Porro C, Carusio N, Favre J, Richard V, Henrion D, Martínez MC, Andriantsitohaina R. Sonic hedgehog carried by microparticles corrects endothelial injury through nitric oxide release. FASEB J. 2007;21:2735-2741. doi: 10.1096/fj.07-8079com.
142. Burger D, Montezano AC, Nishigaki N, He Y, Carter A, Touyz RM. Endothelial microparticle formation by angiotensin II is mediated via Ang II receptor type I/NADPH oxidase/Rho kinase pathways targeted to lipid rafts. Arterioscler Thromb Vasc Biol. 2011;31:1898-1907. doi: 10.1161/ATVBAHA.110.222703.
143. Rautou PE, Leroyer AS, Ramkhelawon B, Devue C, Duflaut D, Vion AC, Nalbone G, Castier Y, Leseche G, Lehoux S, Tedgui A, Boulanger CM. Microparticles from human atherosclerotic plaques promote endothelial ICAM-1-dependent monocyte adhesion and transendothelial migration. Circ Res. 2011;108:335-343. doi: 10.1161/CIRCRESAHA.110.237420.
144. Happonen KE, Tran S, Mörgelin M, Prince R, Calzavarini S, Angelillo-Scherrer A, Dahlbäck B. The Gas6-Axl protein interaction mediates endothelial uptake of platelet microparticles. J Biol Chem. 2016;291:10586-10601. doi: 10.1074/jbc.M115.699058.
145. Ridder K, Keller S, Dams M, et al. Extracellular vesicle-mediated transfer of genetic information between the hematopoietic system and the brain in response to inflammation. PLoS Biol. 2014;12:e1001874. doi: 10.1371/journal.pbio.1001874.
146. Lai CP, Kim EY, Badr CE, Weissleder R, Mempel TR, Tannous BA, Breakefield XO. Visualization and tracking of tumour extracellular vesicle delivery and RNA translation using multiplexed reporters. Nat Commun. 2015;6:7029. doi: 10.1038/ncomms8029.
147. Lai CP, Mardini O, Ericsson M, Prabhakar S, Maguire C, Chen JW, Tannous BA, Breakefield XO. Dynamic biodistribution of extracellular vesicles in vivo using a multimodal imaging reporter. ACS Nano. 2014;8:483-494. doi: 10.1021/nn404945r.
148. Busato A, Bonafede R, Bontempi P, Scambi I, Schiaffino L, Benati D, Malatesta M, Sbarbati A, Marzola P, Mariotti R. Labeling and magnetic resonance imaging of exosomes isolated from adipose stem cells. Curr Protoc Cell Biol. 2017;75:3.44.1-3.44.15. doi: 10.1002/cpcb.23.
149. O'Halloran SM, Heaf DP. Accident and emergency department attendance by asthmatic children. Thorax. 1989;44:700-705.
150. Hu L, Wickline SA, Hood JL. Magnetic resonance imaging of melanoma exosomes in lymph nodes. Magn Reson Med. 2014;74:266-271.
151. Garikipati VN, Jadhav S, Pal L, Prakash P, Dikshit M, Nityanand S. Mesenchymal stem cells from fetal heart attenuate myocardial injury after infarction: an in vivo serial pinhole gated SPECT-CT study in rats. PLoS One. 2014;9:e100982. doi: 10.1371/journal.pone.0100982.
152. Saunderson SC, Dunn AC, Crocker PR, McLellan AD. CD169 mediates the capture of exosomes in spleen and lymph node. Blood. 2014;123:208-216. doi: 10.1182/blood-2013-03-489732.
153. Rand ML, Wang H, Bang KW, Packham MA, Freedman J. Rapid clearance of procoagulant platelet-derived microparticles from the circulation of rabbits. J Thromb Haemost. 2006;4:1621-1623. doi: 10.1111/j.1538-7836.2006.02011.x.
154. Willekens FL, Werre JM, Kruijt JK, Roerdinkholder-Stoelwinder B, Groenen-Döpp YA, van den Bos AG, Bosman GJ, van Berkel TJ. Liver Kupffer cells rapidly remove red blood cell-derived vesicles from the circulation by scavenger receptors. Blood. 2005;105:2141-2145. doi: 10.1182/blood-2004-04-1578.
155. 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. doi: 10.1016/j.jbiotec.2013.03.013.
156. Rank A, Nieuwland R, Crispin A, Grützner S, Iberer M, Toth B, Pihusch R. Clearance of platelet microparticles in vivo. Platelets. 2011;22:111-116. doi: 10.3109/09537104.2010.520373.
157. Ishigami S, Ohtsuki S, Tarui S, et al. Intracoronary autologous cardiac progenitor cell transfer in patients with hypoplastic left heart syndrome: the TICAP prospective phase 1 controlled trial. Circ Res. 2015;116:653-664. doi: 10.1161/CIRCRESAHA.116.304671.
158. Platt MO, Wilder CL, Wells A, Griffith LG, Lauffenburger DA. Multipathway kinase signatures of multipotent stromal cells are predictive for osteogenic differentiation: tissue-specific stem cells. Stem Cells. 2009;27:2804-2814. doi: 10.1002/stem.215.
159. Agarwal U, Smith AW, French KM, et al. Age-dependent effect of pediatric cardiac progenitor cells after juvenile heart failure. Stem Cells Transl Med. 2016;5:883-892. doi: 10.5966/sctm.2015-0241.
160. Mayourian J, Cashman TJ, Ceholski DK, Johnson BV, Sachs D, Kaji DA, Sahoo S, Hare JM, Hajjar RJ, Sobie EA, Costa KD. Experimental and computational insight into human mesenchymal stem cell paracrine signaling and heterocellular coupling effects on cardiac contractility and arrhythmogenicity. Circ Res. 2017;121:411-423. doi: 10.1161/CIRCRESAHA.117.310796.
161. Emanueli C, Shearn AI, Laftah A, Fiorentino F, Reeves BC, Beltrami C, Mumford A, Clayton A, Gurney M, Shantikumar S, Angelini GD. Coronary artery-bypass-graft surgery increases the plasma concentration of exosomes carrying a cargo of cardiac microRNAs: an example of exosome trafficking out of the human heart with potential for cardiac biomarker discovery. PLoS One. 2016;11:e0154274. doi: 10.1371/journal.pone.0154274.
162. Jansen F, Yang X, Proebsting S, Hoelscher M, Przybilla D, Baumann K, Schmitz T, Dolf A, Endl E, Franklin BS, Sinning JM, Vasa-Nicotera M, Nickenig G, Werner N. MicroRNA expression in circulating microvesicles predicts cardiovascular events in patients with coronary artery disease. J Am Heart Assoc. 2014;3:e001249. doi: 10.1161/JAHA.114.001249.
163. Bi S, Wang C, Jin Y, Lv Z, Xing X, Lu Q. Correlation between serum exosome derived miR-208a and acute coronary syndrome. Int J Clin Exp Med. 2015;8:4275-4280.
164. Matsumoto S, Sakata Y, Suna S, Nakatani D, Usami M, Hara M, Kitamura T, Hamasaki T, Nanto S, Kawahara Y, Komuro I. Circulating p53-responsive microRNAs are predictive indicators of heart failure after acute myocardial infarction. Circ Res. 2013;113:322-326. doi: 10.1161/CIRCRESAHA.113.301209.
165. Kuosmanen SM, Hartikainen J, Hippeläinen M, Kokki H, Levonen AL, Tavi P. MicroRNA profiling of pericardial fluid samples from patients with heart failure. PLoS One. 2015;10:e0119646. doi: 10.1371/journal.pone.0119646.
166. Besse B, Charrier M, Lapierre V, et al. Dendritic cell-derived exosomes as maintenance immunotherapy after first line chemotherapy in NSCLC. Oncoimmunology. 2016;5:e1071008. doi: 10.1080/2162402X. 2015.1071008.
167. Escudier B, Dorval T, Chaput N, et al. Vaccination of metastatic melanoma patients with autologous dendritic cell (DC) derived-exosomes: results of the first phase I clinical trial. J Transl Med. 2005;3:10. doi: 10.1186/1479-5876-3-10.