13. Abels ER, Breakefield XO (2016) Introduction
to extracellular vesicles: biogenesis, RNA cargo
selection, content, release, and uptake. Cell
Mol Neurobiol 36:301–312
14. Tricarico C, Clancy J, D’Souza-Schorey C
(2017) Biology and biogenesis of shed microvesicles. Small GTPases 8:220–232
15. Pegtel DM, Peferoen L, Amor S (2014) Extracellular vesicles as modulators of cell-to-cell
communication in the healthy and diseased
brain. Philos Trans R Soc Lond B Biol Sci.
https://doi.org/10.1098/rstb.2013.0516
16. Greening DW, Xu R, Ji H, Tauro BJ, Simpson
RJ (2015) A protocol for exosome isolation
and characterization: evaluation of ultracentrifugation, density-gradient separation, and
immunoaffinity capture methods. Humana
Press, New York, pp 179–209
17. Kumar D, Gupta D, Shankar S, Srivastava RK
(2015) Biomolecular characterization of exosomes released from cancer stem cells: possible
implications for biomarker and treatment of
cancer. Oncotarget 6:3280–3291
18. Raposo G, Stoorvogel W (2013) Extracellular
vesicles: exosomes, microvesicles, and friends. J
Cell Biol 200:373–383
19. Van Niel G, D’Angelo G, Raposo G (2018)
Shedding light on the cell biology of extracellular vesicles. Nat Rev Mol Cell Biol
19:213–228
20. Akuma P, Okagu OD, Udenigwe CC (2019)
Naturally occurring exosome vesicles as potential delivery vehicle for bioactive compounds.
Front Sustain Food Syst 3:23
21. He C, Zheng S, Luo Y, Wang B (2018) Exosome theranostics: biology and translational
medicine. Theranostics 8:237–255
22. Aryani A, Denecke B (2016) Exosomes as a
nanodelivery system: a key to the future of
neuromedicine? Mol Neurobiol 53:818–834
23. Pascucci L, Cocce ` V, Bonomi A et al (2014)
Paclitaxel is incorporated by mesenchymal stromal cells and released in exosomes that inhibit
in vitro tumor growth: a new approach for drug
delivery. J Control Release 192:262–270
24. Gomari H, Forouzandeh Moghadam M, Soleimani M (2018) Targeted cancer therapy using
engineered exosome as a natural drug delivery
vehicle. Onco Targets Ther 11:5753–5762
25. Kalani A, Chaturvedi P (2017) Curcuminprimed and curcumin-loaded exosomes:
potential neural therapy. Neural Regen Res
12:205–206
26. Haney MJ, Klyachko NL, Zhao Y et al (2015)
Exosomes as drug delivery vehicles for Parkinson’s disease therapy. J Control Release
207:18–30
27. Faruqu FN, Xu L, Al-Jamal KT (2018) Preparation of exosomes for siRNA delivery to cancer cells. J Vis Exp. https://doi.org/10.3791/
58814
28. Beuzelin D, Kaeffer B (2018) Exosomes and
miRNA-loaded biomimetic nanovehicles, a
focus on their potentials preventing type-2diabetes linked to metabolic syndrome. Front
Immunol 9:2711
29. Goh WJ, Zou S, Ong WY, Torta F, Alexandra
AF, Schiffelers RM, Storm G, Wang J-W,
Czarny B, Pastorin G (2017) Bioinspired cellderived nanovesicles versus exosomes as drug
delivery systems: a cost-effective alternative. Sci
Rep 7:14322
30. The ´ry C, Amigorena S, Raposo G, Clayton A
(2006) Isolation and characterization of exosomes from cell culture supernatants and
biological fluids. Curr Protoc Cell Biol
30:3.22.1–3.22.29
31. Yu L-L, Zhu J, Liu J-X, Jiang F, Ni W-K, Qu
L-S, Ni R-Z, Lu C-H, Xiao M-B (2018) A
comparison of traditional and novel methods
for the separation of exosomes from human
samples. Biomed Res Int 2018:1–9
32. Patel GK, Khan MA, Zubair H, Srivastava SK,
Khushman M, Singh S, Singh AP (2019) Comparative analysis of exosome isolation methods
using culture supernatant for optimum yield,
purity and downstream applications. Sci Rep
9:5335
33. Konoshenko MY, Lekchnov EA, Vlassov AV,
Laktionov PP (2018) Isolation of extracellular
vesicles: general methodologies and latest
trends. Biomed Res Int 2018:1–27
34. Wang J-W, Zhang Y-N, Sze S et al (2017)
Lowering low-density lipoprotein particles in
plasma using dextran sulphate co-precipitates
procoagulant extracellular vesicles. Int J Mol
Sci 19:94
35. Jo W, Jeong D, Kim J, Cho S, Jang SC, Han C,
Kang JY, Gho YS, Park J (2014) Microfluidic
fabrication of cell-derived nanovesicles as
endogenous RNA carriers. Lab Chip
14:1261–1269
36. Yoon J, Jo W, Jeong D, Kim J, Jeong H, Park J
(2015) Generation of nanovesicles with sliced
cellular membrane fragments for exogenous
material delivery. Biomaterials 59:12–20
37. Jang SC, Kim OY, Yoon CM, Choi D-S, Roh
T-Y, Park J, Nilsson J, Lo ¨tvall J, Kim Y-K, Gho
YS (2013) Bioinspired exosome-mimetic nanovesicles for targeted delivery of chemotherapeutics to malignant tumors. ACS Nano
7:7698–7710
38. Jo W, Kim J, Yoon J, Jeong D, Cho S, Jeong H,
Yoon YJ, Kim SC, Gho YS, Park J (2014)
168
Yi-Hsuan Ou et al.
to extracellular vesicles: biogenesis, RNA cargo
selection, content, release, and uptake. Cell
Mol Neurobiol 36:301–312
14. Tricarico C, Clancy J, D’Souza-Schorey C
(2017) Biology and biogenesis of shed microvesicles. Small GTPases 8:220–232
15. Pegtel DM, Peferoen L, Amor S (2014) Extracellular vesicles as modulators of cell-to-cell
communication in the healthy and diseased
brain. Philos Trans R Soc Lond B Biol Sci.
https://doi.org/10.1098/rstb.2013.0516
16. Greening DW, Xu R, Ji H, Tauro BJ, Simpson
RJ (2015) A protocol for exosome isolation
and characterization: evaluation of ultracentrifugation, density-gradient separation, and
immunoaffinity capture methods. Humana
Press, New York, pp 179–209
17. Kumar D, Gupta D, Shankar S, Srivastava RK
(2015) Biomolecular characterization of exosomes released from cancer stem cells: possible
implications for biomarker and treatment of
cancer. Oncotarget 6:3280–3291
18. Raposo G, Stoorvogel W (2013) Extracellular
vesicles: exosomes, microvesicles, and friends. J
Cell Biol 200:373–383
19. Van Niel G, D’Angelo G, Raposo G (2018)
Shedding light on the cell biology of extracellular vesicles. Nat Rev Mol Cell Biol
19:213–228
20. Akuma P, Okagu OD, Udenigwe CC (2019)
Naturally occurring exosome vesicles as potential delivery vehicle for bioactive compounds.
Front Sustain Food Syst 3:23
21. He C, Zheng S, Luo Y, Wang B (2018) Exosome theranostics: biology and translational
medicine. Theranostics 8:237–255
22. Aryani A, Denecke B (2016) Exosomes as a
nanodelivery system: a key to the future of
neuromedicine? Mol Neurobiol 53:818–834
23. Pascucci L, Cocce ` V, Bonomi A et al (2014)
Paclitaxel is incorporated by mesenchymal stromal cells and released in exosomes that inhibit
in vitro tumor growth: a new approach for drug
delivery. J Control Release 192:262–270
24. Gomari H, Forouzandeh Moghadam M, Soleimani M (2018) Targeted cancer therapy using
engineered exosome as a natural drug delivery
vehicle. Onco Targets Ther 11:5753–5762
25. Kalani A, Chaturvedi P (2017) Curcuminprimed and curcumin-loaded exosomes:
potential neural therapy. Neural Regen Res
12:205–206
26. Haney MJ, Klyachko NL, Zhao Y et al (2015)
Exosomes as drug delivery vehicles for Parkinson’s disease therapy. J Control Release
207:18–30
27. Faruqu FN, Xu L, Al-Jamal KT (2018) Preparation of exosomes for siRNA delivery to cancer cells. J Vis Exp. https://doi.org/10.3791/
58814
28. Beuzelin D, Kaeffer B (2018) Exosomes and
miRNA-loaded biomimetic nanovehicles, a
focus on their potentials preventing type-2diabetes linked to metabolic syndrome. Front
Immunol 9:2711
29. Goh WJ, Zou S, Ong WY, Torta F, Alexandra
AF, Schiffelers RM, Storm G, Wang J-W,
Czarny B, Pastorin G (2017) Bioinspired cellderived nanovesicles versus exosomes as drug
delivery systems: a cost-effective alternative. Sci
Rep 7:14322
30. The ´ry C, Amigorena S, Raposo G, Clayton A
(2006) Isolation and characterization of exosomes from cell culture supernatants and
biological fluids. Curr Protoc Cell Biol
30:3.22.1–3.22.29
31. Yu L-L, Zhu J, Liu J-X, Jiang F, Ni W-K, Qu
L-S, Ni R-Z, Lu C-H, Xiao M-B (2018) A
comparison of traditional and novel methods
for the separation of exosomes from human
samples. Biomed Res Int 2018:1–9
32. Patel GK, Khan MA, Zubair H, Srivastava SK,
Khushman M, Singh S, Singh AP (2019) Comparative analysis of exosome isolation methods
using culture supernatant for optimum yield,
purity and downstream applications. Sci Rep
9:5335
33. Konoshenko MY, Lekchnov EA, Vlassov AV,
Laktionov PP (2018) Isolation of extracellular
vesicles: general methodologies and latest
trends. Biomed Res Int 2018:1–27
34. Wang J-W, Zhang Y-N, Sze S et al (2017)
Lowering low-density lipoprotein particles in
plasma using dextran sulphate co-precipitates
procoagulant extracellular vesicles. Int J Mol
Sci 19:94
35. Jo W, Jeong D, Kim J, Cho S, Jang SC, Han C,
Kang JY, Gho YS, Park J (2014) Microfluidic
fabrication of cell-derived nanovesicles as
endogenous RNA carriers. Lab Chip
14:1261–1269
36. Yoon J, Jo W, Jeong D, Kim J, Jeong H, Park J
(2015) Generation of nanovesicles with sliced
cellular membrane fragments for exogenous
material delivery. Biomaterials 59:12–20
37. Jang SC, Kim OY, Yoon CM, Choi D-S, Roh
T-Y, Park J, Nilsson J, Lo ¨tvall J, Kim Y-K, Gho
YS (2013) Bioinspired exosome-mimetic nanovesicles for targeted delivery of chemotherapeutics to malignant tumors. ACS Nano
7:7698–7710
38. Jo W, Kim J, Yoon J, Jeong D, Cho S, Jeong H,
Yoon YJ, Kim SC, Gho YS, Park J (2014)
168
Yi-Hsuan Ou et al.