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delivery system: the anti-inflammatory activity of curcumin is enhanced when encapsulated in
exosomes. Mol. Ther. 18(9), 1606–1614 (2010)
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carriers: from cellular waste elimination to therapeutic applications. Drug Deliv. Transl. Res.
4(1), 31–37 (2014)
10. L. Barile, V. Lionetti, E. Cervio, M. Matteucci, M. Gherghiceanu, L.M. Popescu et al.,
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biodistribution of polymeric nanoparticles. Mol. Pharm. 5(4), 505–515 (2008)
12. T.K. Jain, M.K. Reddy, M.A. Morales, D.L. Leslie-Pelecky, V. Labhasetwar, Biodistribution,
clearance, and biocompatibility of iron oxide magnetic nanoparticles in rats. Mol. Pharm. 5
(2), 316–327 (2008)
13. S.C. Jang, O.Y. Kim, C.M. Yoon, D.S. Choi, T.Y. Roh, J. Park et al., Bioinspired
exosome-mimetic nanovesicles for targeted delivery of chemotherapeutics to malignant
tumors. ACS Nano 7(9), 7698–7710 (2013)
14. C.P. Lai, E.Y. Kim, C.E. Badr, R. Weissleder, T.R. Mempel, B.A. Tannous et al.,
Visualization and tracking of tumour extracellular vesicle delivery and RNA translation using
multiplexed reporters. Nat. Commun. 6, 7029 (2015)
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biodistribution of extracellular vesicles in vivo using a multimodal imaging reporter. ACS
Nano 8(1), 483–494 (2014)
16. O.G. De Jong, B.W. Van Balkom, R.M. Schiffelers, C.V. Bouten, M.C. Verhaar, Extracellular
vesicles: potential roles in regenerative medicine. Front. Immunol. 5, 608 (2014)
17. D. Orlic, J. Kajstura, S. Chimenti, I. Jakoniuk, S.M. Anderson, B. Li et al., Bone marrow cells
regenerate infarcted myocardium. Nature 410(6829), 701–705 (2001)
18. C. Stamm, B. Westphal, H.-D. Kleine, M. Petzsch, C. Kittner, H. Klinge et al., Autologous
bone-marrow stem-cell transplantation for myocardial regeneration. Lancet 361(9351), 45–46
(2003)
19. J.G. Shake, P.J. Gruber, W.A. Baumgartner, G. Senechal, J. Meyers, J.M. Redmond et al.,
Mesenchymal stem cell implantation in a swine myocardial infarct model: engraftment and
functional effects. Ann. Thorac. Surg. 73(6), 1919–1926 (2002)
20. P.R. Baraniak, T.C. McDevitt, Stem cell paracrine actions and tissue regeneration. Regen.
Med. 5(1), 121–143 (2010)
21. T.J. Burdon, A. Paul, N. Noiseux, S. Prakash, D. Shum-Tim, Bone marrow stem cell derived
paracrine factors for regenerative medicine: current perspectives and therapeutic potential.
Bone Marrow. Res. 2011, 207326 (2011)
22. M. Mirotsou, T.M. Jayawardena, J. Schmeckpeper, M. Gnecchi, V.J. Dzau, Paracrine
mechanisms of stem cell reparative and regenerative actions in the heart. J. Mol. Cell. Cardiol.
50(2), 280–289 (2011)
23. M. Gnecchi, Z. Zhang, A. Ni, V.J. Dzau, Paracrine mechanisms in adult stem cell signaling
and therapy. Circ. Res. 103(11), 1204–1219 (2008)
24. J.R. Lavoie, M. Rosu-Myles, Uncovering the secretes of mesenchymal stem cells. Biochimie
95(12), 2212–2221 (2013)
25. T. Lener, M. Gimona, L. Aigner, V. Börger, E. Buzas, G. Camussi et al., Applying
extracellular vesicles based therapeutics in clinical trials–an ISEV position paper. J. Extracell.
Vesicles. 4, 30087 (2015)
26. J.L. Hood, R.S. San, S.A. Wickline, Exosomes released by melanoma cells prepare sentinel
lymph nodes for tumor metastasis. Cancer Res. 71(11), 3792–3801 (2011)
150
H. Choi and D. W. Hwang
mouse brain by systemic injection of targeted exosomes. Nat. Biotechnol. 29(4), 341–345
(2011)
8. D. Sun, X. Zhuang, X. Xiang, Y. Liu, S. Zhang, C. Liu et al., A novel nanoparticle drug
delivery system: the anti-inflammatory activity of curcumin is enhanced when encapsulated in
exosomes. Mol. Ther. 18(9), 1606–1614 (2010)
9. K. Hagiwara, T. Ochiya, N. Kosaka, A paradigm shift for extracellular vesicles as small RNA
carriers: from cellular waste elimination to therapeutic applications. Drug Deliv. Transl. Res.
4(1), 31–37 (2014)
10. L. Barile, V. Lionetti, E. Cervio, M. Matteucci, M. Gherghiceanu, L.M. Popescu et al.,
Extracellular vesicles from human cardiac progenitor cells inhibit cardiomyocyte apoptosis
and improve cardiac function after myocardial infarction. Cardiovasc. Res. 103(4), 530–541
(2014)
11. F. Alexis, E. Pridgen, L.K. Molnar, O.C. Farokhzad, Factors affecting the clearance and
biodistribution of polymeric nanoparticles. Mol. Pharm. 5(4), 505–515 (2008)
12. T.K. Jain, M.K. Reddy, M.A. Morales, D.L. Leslie-Pelecky, V. Labhasetwar, Biodistribution,
clearance, and biocompatibility of iron oxide magnetic nanoparticles in rats. Mol. Pharm. 5
(2), 316–327 (2008)
13. S.C. Jang, O.Y. Kim, C.M. Yoon, D.S. Choi, T.Y. Roh, J. Park et al., Bioinspired
exosome-mimetic nanovesicles for targeted delivery of chemotherapeutics to malignant
tumors. ACS Nano 7(9), 7698–7710 (2013)
14. C.P. Lai, E.Y. Kim, C.E. Badr, R. Weissleder, T.R. Mempel, B.A. Tannous et al.,
Visualization and tracking of tumour extracellular vesicle delivery and RNA translation using
multiplexed reporters. Nat. Commun. 6, 7029 (2015)
15. C.P. Lai, O. Mardini, M. Ericsson, S. Prabhakar, C.A. Maguire, J.W. Chen et al., Dynamic
biodistribution of extracellular vesicles in vivo using a multimodal imaging reporter. ACS
Nano 8(1), 483–494 (2014)
16. O.G. De Jong, B.W. Van Balkom, R.M. Schiffelers, C.V. Bouten, M.C. Verhaar, Extracellular
vesicles: potential roles in regenerative medicine. Front. Immunol. 5, 608 (2014)
17. D. Orlic, J. Kajstura, S. Chimenti, I. Jakoniuk, S.M. Anderson, B. Li et al., Bone marrow cells
regenerate infarcted myocardium. Nature 410(6829), 701–705 (2001)
18. C. Stamm, B. Westphal, H.-D. Kleine, M. Petzsch, C. Kittner, H. Klinge et al., Autologous
bone-marrow stem-cell transplantation for myocardial regeneration. Lancet 361(9351), 45–46
(2003)
19. J.G. Shake, P.J. Gruber, W.A. Baumgartner, G. Senechal, J. Meyers, J.M. Redmond et al.,
Mesenchymal stem cell implantation in a swine myocardial infarct model: engraftment and
functional effects. Ann. Thorac. Surg. 73(6), 1919–1926 (2002)
20. P.R. Baraniak, T.C. McDevitt, Stem cell paracrine actions and tissue regeneration. Regen.
Med. 5(1), 121–143 (2010)
21. T.J. Burdon, A. Paul, N. Noiseux, S. Prakash, D. Shum-Tim, Bone marrow stem cell derived
paracrine factors for regenerative medicine: current perspectives and therapeutic potential.
Bone Marrow. Res. 2011, 207326 (2011)
22. M. Mirotsou, T.M. Jayawardena, J. Schmeckpeper, M. Gnecchi, V.J. Dzau, Paracrine
mechanisms of stem cell reparative and regenerative actions in the heart. J. Mol. Cell. Cardiol.
50(2), 280–289 (2011)
23. M. Gnecchi, Z. Zhang, A. Ni, V.J. Dzau, Paracrine mechanisms in adult stem cell signaling
and therapy. Circ. Res. 103(11), 1204–1219 (2008)
24. J.R. Lavoie, M. Rosu-Myles, Uncovering the secretes of mesenchymal stem cells. Biochimie
95(12), 2212–2221 (2013)
25. T. Lener, M. Gimona, L. Aigner, V. Börger, E. Buzas, G. Camussi et al., Applying
extracellular vesicles based therapeutics in clinical trials–an ISEV position paper. J. Extracell.
Vesicles. 4, 30087 (2015)
26. J.L. Hood, R.S. San, S.A. Wickline, Exosomes released by melanoma cells prepare sentinel
lymph nodes for tumor metastasis. Cancer Res. 71(11), 3792–3801 (2011)
150
H. Choi and D. W. Hwang