Current Strategies for Promoting the Large-scale Production of Exosomes

Zaborowski, M.P.; Balaj, L.; Breakefield, X.O.; Lai, C.P. Extracellular vesicles: Composition, biological relevance, and methods of study. Bioscience, 2015, 65(8), 783-797.
[http://dx.doi.org/10.1093/biosci/biv084] [PMID: 26955082]

Jeppesen, D.K.; Fenix, A.M.; Franklin, J.L.; Higginbotham, J.N.; Zhang, Q.; Zimmerman, L.J.; Liebler, D.C.; Ping, J.; Liu, Q.; Evans, R.; Fissell, W.H.; Patton, J.G.; Rome, L.H.; Burnette, D.T.; Coffey, R.J. Reassessment of Exosome Composition. Cell, 2019, 177(2), 428-445.e18.
[http://dx.doi.org/10.1016/j.cell.2019.02.029] [PMID: 30951670]

Doyle, L.; Wang, M. Overview of Extracellular vesicles, their origin, composition, purpose, and methods for exosome isolation and analysis. Cells, 2019, 8(7), 727.
[http://dx.doi.org/10.3390/cells8070727] [PMID: 31311206]

Théry, C.; Witwer, K.W.; Aikawa, E.; Alcaraz, M.J.; Anderson, J.D.; Andriantsitohaina, R.; Antoniou, A.; Arab, T.; Archer, F.; Atkin-Smith, G.K.; Ayre, D.C.; Bach, J.M.; Bachurski, D.; Baharvand, H.; Balaj, L.; Baldacchino, S.; Bauer, N.N.; Baxter, A.A.; Bebawy, M.; Beckham, C.; Bedina Zavec, A.; Benmoussa, A.; Berardi, A.C.; Bergese, P.; Bielska, E.; Blenkiron, C.; Bobis-Wozowicz, S.; Boilard, E.; Boireau, W.; Bongiovanni, A.; Borràs, F.E.; Bosch, S.; Boulanger, C.M.; Breakefield, X.; Breglio, A.M.; Brennan, M.; Brigstock, D.R.; Brisson, A.; Broekman, M.L.; Bromberg, J.F.; Bryl-Górecka, P.; Buch, S.; Buck, A.H.; Burger, D.; Busatto, S.; Buschmann, D.; Bussolati, B.; Buzás, E.I.; Byrd, J.B.; Camussi, G.; Carter, D.R.; Caruso, S.; Chamley, L.W.; Chang, Y.T.; Chen, C.; Chen, S.; Cheng, L.; Chin, A.R.; Clayton, A.; Clerici, S.P.; Cocks, A.; Cocucci, E.; Coffey, R.J.; Cordeiro-da-Silva, A.; Couch, Y.; Coumans, F.A.; Coyle, B.; Crescitelli, R.; Criado, M.F.; D’Souza-Schorey, C.; Das, S.; Datta Chaudhuri, A.; de Candia, P.; De Santana, E.F.; De Wever, O.; Del Portillo, H.A.; Demaret, T.; Deville, S.; Devitt, A.; Dhondt, B.; Di Vizio, D.; Dieterich, L.C.; Dolo, V.; Dominguez Rubio, A.P.; Dominici, M.; Dourado, M.R.; Driedonks, T.A.; Duarte, F.V.; Duncan, H.M.; Eichenberger, R.M.; Ekström, K.; El Andaloussi, S.; Elie-Caille, C.; Erdbrügger, U.; Falcón-Pérez, J.M.; Fatima, F.; Fish, J.E.; Flores-Bellver, M.; Försönits, A.; Frelet-Barrand, A.; Fricke, F.; Fuhrmann, G.; Gabrielsson, S.; Gámez-Valero, A.; Gardiner, C.; Gärtner, K.; Gaudin, R.; Gho, Y.S.; Giebel, B.; Gilbert, C.; Gimona, M.; Giusti, I.; Goberdhan, D.C.; Görgens, A.; Gorski, S.M.; Greening, D.W.; Gross, J.C.; Gualerzi, A.; Gupta, G.N.; Gustafson, D.; Handberg, A.; Haraszti, R.A.; Harrison, P.; Hegyesi, H.; Hendrix, A.; Hill, A.F.; Hochberg, F.H.; Hoffmann, K.F.; Holder, B.; Holthofer, H.; Hosseinkhani, B.; Hu, G.; Huang, Y.; Huber, V.; Hunt, S.; Ibrahim, A.G.; Ikezu, T.; Inal, J.M.; Isin, M.; Ivanova, A.; Jackson, H.K.; Jacobsen, S.; Jay, S.M.; Jayachandran, M.; Jenster, G.; Jiang, L.; Johnson, S.M.; Jones, J.C.; Jong, A.; Jovanovic-Talisman, T.; Jung, S.; Kalluri, R.; Kano, S.I.; Kaur, S.; Kawamura, Y.; Keller, E.T.; Khamari, D.; Khomyakova, E.; Khvorova, A.; Kierulf, P.; Kim, K.P.; Kislinger, T.; Klingeborn, M.; Klinke, D.J., II; Kornek, M. Kosanović M.M.; Kovács, Á. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): A position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. J. Extracell. Vesicles, 2018, 7(1), 1535750.
[PMID: 30637094]

Wang, J.; Yue, B.L.; Huang, Y.Z.; Lan, X.Y.; Liu, W.J.; Chen, H. Exosomal RNAs: Novel potential biomarkers for diseases—A review. Int. J. Mol. Sci., 2022, 23(5), 2461.
[http://dx.doi.org/10.3390/ijms23052461] [PMID: 35269604]

Wiklander, O.P.B.; Brennan, M.Á.; Lötvall, J.; Breakefield, X.O.E.L; Andaloussi, S. S. Advances in therapeutic applications of extracellular vesicles. Sci. Transl. Med., 2019, 11(492), eaav8521.
[http://dx.doi.org/10.1126/scitranslmed.aav8521] [PMID: 31092696]

Nassar, W.; El-Ansary, M.; Sabry, D.; Mostafa, M.A.; Fayad, T.; Kotb, E.; Temraz, M.; Saad, A.N.; Essa, W.; Adel, H. Umbilical cord mesenchymal stem cells derived extracellular vesicles can safely ameliorate the progression of chronic kidney diseases. Biomater. Res., 2016, 20(1), 21.
[http://dx.doi.org/10.1186/s40824-016-0068-0] [PMID: 27499886]

Sun, X.; Meng, H.; Wan, W.; Xie, M.; Wen, C. Application potential of stem/progenitor cell-derived extracellular vesicles in renal diseases. Stem Cell Res. Ther., 2019, 10(1), 8.
[http://dx.doi.org/10.1186/s13287-018-1097-5] [PMID: 30616603]

He, C.; Zheng, S.; Luo, Y.; Wang, B. Exosome theranostics: Biology and translational medicine. Theranostics, 2018, 8(1), 237-255.
[http://dx.doi.org/10.7150/thno.21945] [PMID: 29290805]

Qin, B.; Zhang, Q.; Chen, D.; Yu, H.Y.; Luo, A.X.; Suo, L.P.; Cai, Y.; Cai, D.Y.; Luo, J.; Huang, J.F.; Xiong, K. Extracellular vesicles derived from mesenchymal stem cells: A platform that can be engineered. Histol. Histopathol., 2021, 36(6), 615-632.
[PMID: 33398872]

Kalluri, R.; LeBleu, V.S. The biology, function, and biomedical applications of exosomes. Science, 2020, 367(6478), eaau6977.
[http://dx.doi.org/10.1126/science.aau6977] [PMID: 32029601]

Henne, W.M.; Buchkovich, N.J.; Emr, S.D. The ESCRT Pathway. Dev. Cell, 2011, 21(1), 77-91.
[http://dx.doi.org/10.1016/j.devcel.2011.05.015] [PMID: 21763610]

Raiborg, C.; Wesche, J.; Malerød, L.; Stenmark, H. Flat clathrin coats on endosomes mediate degradative protein sorting by scaffolding Hrs in dynamic microdomains. J. Cell Sci., 2006, 119(12), 2414-2424.
[http://dx.doi.org/10.1242/jcs.02978] [PMID: 16720641]

Zhang, Y.; Liu, Y.; Liu, H.; Tang, W.H. Exosomes: biogenesis, biologic function and clinical potential. Cell Biosci., 2019, 9(1), 19.
[http://dx.doi.org/10.1186/s13578-019-0282-2] [PMID: 30815248]

Wollert, T.; Hurley, J.H. Molecular mechanism of multivesicular body biogenesis by ESCRT complexes. Nature, 2010, 464(7290), 864-869.
[http://dx.doi.org/10.1038/nature08849] [PMID: 20305637]

Isaac, R.; Reis, F.C.G.; Ying, W.; Olefsky, J.M. Exosomes as mediators of intercellular crosstalk in metabolism. Cell Metab., 2021, 33(9), 1744-1762.
[http://dx.doi.org/10.1016/j.cmet.2021.08.006] [PMID: 34496230]

Bebelman, M.P.; Smit, M.J.; Pegtel, D.M.; Baglio, S.R. Biogenesis and function of extracellular vesicles in cancer. Pharmacol. Ther., 2018, 188, 1-11.
[http://dx.doi.org/10.1016/j.pharmthera.2018.02.013] [PMID: 29476772]

Hao, Y.; Song, H.; Zhou, Z.; Chen, X.; Li, H.; Zhang, Y.; Wang, J.; Ren, X.; Wang, X. Promotion or inhibition of extracellular vesicle release: Emerging therapeutic opportunities. J. Control. Release, 2021, 340, 136-148.
[http://dx.doi.org/10.1016/j.jconrel.2021.10.019] [PMID: 34695524]

Hessvik, N.P.; Llorente, A. Current knowledge on exosome biogenesis and release. Cell. Mol. Life Sci., 2018, 75(2), 193-208.
[http://dx.doi.org/10.1007/s00018-017-2595-9] [PMID: 28733901]

Luo, L.; Wu, Z.; Wang, Y.; Li, H. Regulating the production and biological function of small extracellular vesicles: current strategies, applications and prospects. J. Nanobiotechnology, 2021, 19(1), 422.
[http://dx.doi.org/10.1186/s12951-021-01171-1] [PMID: 34906146]

Jafari, D.; Malih, S.; Eini, M.; Jafari, R.; Gholipourmalekabadi, M.; Sadeghizadeh, M.; Samadikuchaksaraei, A. Improvement, scaling-up, and downstream analysis of exosome production. Crit. Rev. Biotechnol., 2020, 40(8), 1098-1112.
[http://dx.doi.org/10.1080/07388551.2020.1805406] [PMID: 32772758]

Kojima, R.; Bojar, D.; Rizzi, G.; Hamri, G.C.E.; El-Baba, M.D.; Saxena, P.; Ausländer, S.; Tan, K.R.; Fussenegger, M. Designer exosomes produced by implanted cells intracerebrally deliver therapeutic cargo for Parkinson’s disease treatment. Nat. Commun., 2018, 9(1), 1305.
[http://dx.doi.org/10.1038/s41467-018-03733-8] [PMID: 29610454]

Xiong, Y.; Tang, R.; Xu, J.; Jiang, W.; Gong, Z.; Zhang, L.; Li, X.; Ning, Y.; Huang, P.; Xu, J.; Chen, G.; Jin, C.; Li, X.; Qian, H.; Yang, Y. Sequential transplantation of exosomes and mesenchymal stem cells pretreated with a combination of hypoxia and Tongxinluo efficiently facilitates cardiac repair. Stem Cell Res. Ther., 2022, 13(1), 63.
[http://dx.doi.org/10.1186/s13287-022-02736-z] [PMID: 35130979]

Gao, W.; He, R.; Ren, J.; Zhang, W.; Wang, K.; Zhu, L.; Liang, T. Exosomal HMGB1 derived from hypoxia-conditioned bone marrow mesenchymal stem cells increases angiogenesis via the JNK/HIF-1α pathway. FEBS Open Bio, 2021, 11(5), 1364-1373.
[http://dx.doi.org/10.1002/2211-5463.13142] [PMID: 33711197]

He, G.; Peng, X.; Wei, S.; Yang, S.; Li, X.; Huang, M.; Tang, S.; Jin, H.; Liu, J.; Zhang, S.; Zheng, H.; Fan, Q.; Liu, J.; Yang, L.; Li, H. Exosomes in the hypoxic TME: from release, uptake and biofunctions to clinical applications. Mol. Cancer, 2022, 21(1), 19.
[http://dx.doi.org/10.1186/s12943-021-01440-5] [PMID: 35039054]

Kumar, A.; Deep, G. Hypoxia in tumor microenvironment regulates exosome biogenesis: Molecular mechanisms and translational opportunities. Cancer Lett., 2020, 479, 23-30.
[http://dx.doi.org/10.1016/j.canlet.2020.03.017] [PMID: 32201202]

Rosová, I.; Dao, M.; Capoccia, B.; Link, D.; Nolta, J.A. Hypoxic preconditioning results in increased motility and improved therapeutic potential of human mesenchymal stem cells. Stem Cells, 2008, 26(8), 2173-2182.
[http://dx.doi.org/10.1634/stemcells.2007-1104] [PMID: 18511601]

Liu, W.; Li, L.; Rong, Y.; Qian, D.; Chen, J.; Zhou, Z.; Luo, Y.; Jiang, D.; Cheng, L.; Zhao, S.; Kong, F.; Wang, J.; Zhou, Z.; Xu, T.; Gong, F.; Huang, Y.; Gu, C.; Zhao, X.; Bai, J.; Wang, F.; Zhao, W.; Zhang, L.; Li, X.; Yin, G.; Fan, J.; Cai, W. Hypoxic mesenchymal stem cell-derived exosomes promote bone fracture healing by the transfer of miR-126. Acta Biomater., 2020, 103, 196-212.
[http://dx.doi.org/10.1016/j.actbio.2019.12.020] [PMID: 31857259]

Panigrahi, G.K.; Praharaj, P.P.; Peak, T.C.; Long, J.; Singh, R.; Rhim, J.S.; Abd Elmageed, Z.Y.; Deep, G. Hypoxia-induced exosome secretion promotes survival of African-American and Caucasian prostate cancer cells. Sci. Rep., 2018, 8(1), 3853.
[http://dx.doi.org/10.1038/s41598-018-22068-4] [PMID: 29497081]

Gupta, S.; Rawat, S.; Krishnakumar, V.; Rao, E.P.; Mohanty, S. Hypoxia preconditioning elicit differential response in tissue-specific MSCs via immunomodulation and exosomal secretion. Cell Tissue Res., 2022, 388(3), 535-548.
[http://dx.doi.org/10.1007/s00441-022-03615-y] [PMID: 35316374]

Dorayappan, K.D.P.; Wanner, R.; Wallbillich, J.J.; Saini, U.; Zingarelli, R.; Suarez, A.A.; Cohn, D.E.; Selvendiran, K. Hypoxia-induced exosomes contribute to a more aggressive and chemoresistant ovarian cancer phenotype: a novel mechanism linking STAT3/Rab proteins. Oncogene, 2018, 37(28), 3806-3821.
[http://dx.doi.org/10.1038/s41388-018-0189-0] [PMID: 29636548]

Song, Y.; Dou, H.; Li, X.; Zhao, X.; Li, Y.; Liu, D.; Ji, J.; Liu, F.; Ding, L.; Ni, Y.; Hou, Y. Exosomal miR-146a contributes to the enhanced therapeutic efficacy of interleukin-1β-primed mesenchymal stem cells against sepsis. Stem Cells, 2017, 35(5), 1208-1221.
[http://dx.doi.org/10.1002/stem.2564] [PMID: 28090688]

Kim, M.; Shin, D.I.; Choi, B.H.; Min, B.H. Exosomes from IL-1β-primed mesenchymal stem cells inhibited IL-1β- and TNF-α-mediated inflammatory responses in osteoarthritic SW982 cells. Tissue Eng. Regen. Med., 2021, 18(4), 525-536.
[http://dx.doi.org/10.1007/s13770-020-00324-x] [PMID: 33495946]

Nakao, Y.; Fukuda, T.; Zhang, Q.; Sanui, T.; Shinjo, T.; Kou, X.; Chen, C.; Liu, D.; Watanabe, Y.; Hayashi, C.; Yamato, H.; Yotsumoto, K.; Tanaka, U.; Taketomi, T.; Uchiumi, T.; Le, A.D.; Shi, S.; Nishimura, F. Exosomes from TNF-α-treated human gingiva-derived MSCs enhance M2 macrophage polarization and inhibit periodontal bone loss. Acta Biomater., 2021, 122, 306-324.
[http://dx.doi.org/10.1016/j.actbio.2020.12.046] [PMID: 33359765]

Sung, D.K.; Sung, S.I.; Ahn, S.Y.; Chang, Y.S.; Park, W.S. Thrombin preconditioning boosts biogenesis of extracellular vesicles from mesenchymal stem cells and enriches their cargo contents via protease-activated receptor-mediated signaling pathways. Int. J. Mol. Sci., 2019, 20(12), 2899.
[http://dx.doi.org/10.3390/ijms20122899] [PMID: 31197089]

Nakamura, Y.; Kita, S.; Tanaka, Y.; Fukuda, S.; Obata, Y.; Okita, T.; Nishida, H.; Takahashi, Y.; Kawachi, Y.; Tsugawa-Shimizu, Y.; Fujishima, Y.; Nishizawa, H.; Takakura, Y.; Miyagawa, S.; Sawa, Y.; Maeda, N.; Shimomura, I. Adiponectin stimulates exosome release to enhance mesenchymal stem-cell-driven therapy of heart failure in mice. Mol. Ther., 2020, 28(10), 2203-2219.
[http://dx.doi.org/10.1016/j.ymthe.2020.06.026] [PMID: 32652045]

Wang, J.; Bonacquisti, E.E.; Brown, A.D.; Nguyen, J. Boosting the biogenesis and secretion of mesenchymal stem cell-derived exosomes. Cells, 2020, 9(3), 660.
[http://dx.doi.org/10.3390/cells9030660] [PMID: 32182815]

Li, J.; Lee, Y.; Johansson, H.J.; Mäger, I.; Vader, P.; Nordin, J.Z.; Wiklander, O.P.B.; Lehtiö, J.; Wood, M.J.A.; Andaloussi, S.E.L. Serum-free culture alters the quantity and protein composition of neuroblastoma-derived extracellular vesicles. J. Extracell. Vesicles, 2015, 4(1), 26883.
[http://dx.doi.org/10.3402/jev.v4.26883] [PMID: 26022510]

Bost, J.P.; Saher, O.; Hagey, D.; Mamand, D.R.; Liang, X.; Zheng, W.; Corso, G.; Gustafsson, O.; Görgens, A.; Smith, C.I.E.; Zain, R.; El Andaloussi, S.; Gupta, D. Growth media conditions influence the secretion route and release levels of engineered extracellular vesicles. Adv. Healthc. Mater., 2022, 11(5), 2101658.
[http://dx.doi.org/10.1002/adhm.202101658] [PMID: 34773385]

Marzano, M.; Bou-Dargham, M.J.; Cone, A.S.; York, S.; Helsper, S.; Grant, S.C.; Meckes, D.G., Jr; Sang, Q.X.A.; Li, Y. Biogenesis of extracellular vesicles produced from human-stem-cell-derived cortical spheroids exposed to iron oxides. ACS Biomater. Sci. Eng., 2021, 7(3), 1111-1122.
[http://dx.doi.org/10.1021/acsbiomaterials.0c01286] [PMID: 33525864]

Ji, Y.; Han, W.; Fu, X.; Li, J.; Wu, Q.; Wang, Y. Improved small extracellular vesicle secretion of rat adipose-derived stem cells by microgrooved substrates through Upregulation of the ESCRT-III-associated protein alix. Adv. Healthc. Mater., 2021, 10(16), 2100492.
[http://dx.doi.org/10.1002/adhm.202100492] [PMID: 34176241]

Yang, Q.; Nanayakkara, G.K.; Drummer, C.; Sun, Y.; Johnson, C.; Cueto, R.; Fu, H.; Shao, Y.; Wang, L.; Yang, W.Y.; Tang, P.; Liu, L.W.; Ge, S.; Zhou, X.D.; Khan, M.; Wang, H.; Yang, X. Low-intensity ultrasound-induced anti-inflammatory effects are mediated by several new mechanisms including gene induction, immunosuppressor cell promotion, and enhancement of exosome biogenesis and docking. Front. Physiol., 2017, 8, 818.
[http://dx.doi.org/10.3389/fphys.2017.00818] [PMID: 29109687]

Ambattu, L.A.; Ramesan, S.; Dekiwadia, C.; Hanssen, E.; Li, H.; Yeo, L.Y. High frequency acoustic cell stimulation promotes exosome generation regulated by a calcium-dependent mechanism. Commun. Biol., 2020, 3(1), 553.
[http://dx.doi.org/10.1038/s42003-020-01277-6] [PMID: 33020585]

Mayo, J.S.; Kurata, W.E.; O’Connor, K.M.; Pierce, L.M. Oxidative stress alters angiogenic and antimicrobial content of extracellular vesicles and improves flap survival. Plast. Reconstr. Surg. Glob. Open, 2019, 7(12), e2588.
[http://dx.doi.org/10.1097/GOX.0000000000002588] [PMID: 32537316]

Bala, S.; Babuta, M.; Catalano, D.; Saiju, A.; Szabo, G. Alcohol promotes exosome biogenesis and release via modulating rabs and miR-192 expression in human hepatocytes. Front. Cell Dev. Biol., 2022, 9, 787356.
[http://dx.doi.org/10.3389/fcell.2021.787356] [PMID: 35096820]

Mukherjee, S.; Cabrera, M.A.; Boyadjieva, N.I.; Berger, G.; Rousseau, B.; Sarkar, D.K. Alcohol increases exosome release from microglia to promote complement c1q-induced cellular death of proopiomelanocortin neurons in the hypothalamus in a rat model of fetal alcohol spectrum disorders. J. Neurosci., 2020, 40(41), 7965-7979.
[http://dx.doi.org/10.1523/JNEUROSCI.0284-20.2020] [PMID: 32887744]

Mashouri, L.; Yousefi, H.; Aref, A.R.; Ahadi, A.; Molaei, F.; Alahari, S.K. Exosomes: composition, biogenesis, and mechanisms in cancer metastasis and drug resistance. Mol. Cancer, 2019, 18(1), 75.
[http://dx.doi.org/10.1186/s12943-019-0991-5] [PMID: 30940145]

Wei, Y.; Wang, D.; Jin, F.; Bian, Z.; Li, L.; Liang, H.; Li, M.; Shi, L.; Pan, C.; Zhu, D.; Chen, X.; Hu, G.; Liu, Y.; Zhang, C.Y.; Zen, K. Pyruvate kinase type M2 promotes tumour cell exosome release via phosphorylating synaptosome-associated protein 23. Nat. Commun., 2017, 8(1), 14041.
[http://dx.doi.org/10.1038/ncomms14041] [PMID: 28067230]

McAndrews, K.M.; Kalluri, R. Mechanisms associated with biogenesis of exosomes in cancer. Mol. Cancer, 2019, 18(1), 52.
[http://dx.doi.org/10.1186/s12943-019-0963-9] [PMID: 30925917]

Riazifar, M.; Mohammadi, M.R.; Pone, E.J.; Yeri, A.; Lässer, C.; Segaliny, A.I.; McIntyre, L.L.; Shelke, G.V.; Hutchins, E.; Hamamoto, A.; Calle, E.N.; Crescitelli, R.; Liao, W.; Pham, V.; Yin, Y.; Jayaraman, J.; Lakey, J.R.T.; Walsh, C.M.; Van Keuren-Jensen, K.; Lotvall, J.; Zhao, W. Stem cell-derived exosomes as nanotherapeutics for autoimmune and neurodegenerative disorders. ACS Nano, 2019, 13(6), 6670-6688.
[http://dx.doi.org/10.1021/acsnano.9b01004] [PMID: 31117376]

Beyer Nardi, N.; da Silva Meirelles, L. Mesenchymal stem cells: isolation, in vitro expansion and characterization. Handb. Exp. Pharmacol., 2006, 174(174), 249-282.
[http://dx.doi.org/10.1007/3-540-31265-X_11] [PMID: 16370331]

Kalsi, K.; Lawson, C.; Dominguez, M.; Taylor, P.; Yacoub, M.H.; Smolenski, R.T. Regulation of ecto-5'-nucleotidase by TNF-alpha in human endothelial cells. Mol. Cell. Biochem., 2002, 232(1/2), 113-119.
[http://dx.doi.org/10.1023/A:1014806916844] [PMID: 12030367]

Brisevac, D.; Bjelobaba, I.; Bajic, A.; Clarner, T.; Stojiljkovic, M.; Beyer, C.; Andjus, P.; Kipp, M.; Nedeljkovic, N. Regulation of ecto-5'-nucleotidase (CD73) in cultured cortical astrocytes by different inflammatory factors. Neurochem. Int., 2012, 61(5), 681-688.
[http://dx.doi.org/10.1016/j.neuint.2012.06.017] [PMID: 22750273]

Giacomelli, C.; Natali, L.; Nisi, M.; De Leo, M.; Daniele, S.; Costa, B.; Graziani, F.; Gabriele, M.; Braca, A.; Trincavelli, M.L.; Martini, C. Negative effects of a high tumour necrosis factor-α concentration on human gingival mesenchymal stem cell trophism: the use of natural compounds as modulatory agents. Stem Cell Res. Ther., 2018, 9(1), 135.
[http://dx.doi.org/10.1186/s13287-018-0880-7] [PMID: 29751776]

Huang, C.; Luo, W.F.; Ye, Y.F.; Lin, L.; Wang, Z.; Luo, M.H.; Song, Q.D.; He, X.P.; Chen, H.W.; Kong, Y.; Tang, Y.K. Characterization of inflammatory factor-induced changes in mesenchymal stem cell exosomes and sequencing analysis of exosomal microRNAs. World J. Stem Cells, 2019, 11(10), 859-890.
[http://dx.doi.org/10.4252/wjsc.v11.i10.859] [PMID: 31692888]

Sung, D.K.; Chang, Y.S.; Sung, S.I.; Ahn, S.Y.; Park, W.S. Thrombin preconditioning of extracellular vesicles derived from mesenchymal stem cells accelerates cutaneous wound healing by boosting their biogenesis and enriching cargo content. J. Clin. Med., 2019, 8(4), 533.
[http://dx.doi.org/10.3390/jcm8040533] [PMID: 31003433]

Kita, S.; Maeda, N.; Shimomura, I. Interorgan communication by exosomes, adipose tissue, and adiponectin in metabolic syndrome. J. Clin. Invest., 2019, 129(10), 4041-4049.
[http://dx.doi.org/10.1172/JCI129193] [PMID: 31483293]

Obata, Y.; Kita, S.; Koyama, Y.; Fukuda, S.; Takeda, H.; Takahashi, M.; Fujishima, Y.; Nagao, H.; Masuda, S.; Tanaka, Y.; Nakamura, Y.; Nishizawa, H.; Funahashi, T.; Ranscht, B.; Izumi, Y.; Bamba, T.; Fukusaki, E.; Hanayama, R.; Shimada, S.; Maeda, N.; Shimomura, I. Adiponectin/T-cadherin system enhances exosome biogenesis and decreases cellular ceramides by exosomal release. JCI Insight, 2018, 3(8), e99680.
[http://dx.doi.org/10.1172/jci.insight.99680] [PMID: 29669945]

Kita, S.; Shimomura, I. Stimulation of exosome biogenesis by adiponectin, a circulating factor secreted from adipocytes. J. Biochem., 2021, 169(2), 173-179.
[http://dx.doi.org/10.1093/jb/mvaa105] [PMID: 32979268]

Holley, R.J.; Tai, G.; Williamson, A.J.K.; Taylor, S.; Cain, S.A.; Richardson, S.M.; Merry, C.L.R.; Whetton, A.D.; Kielty, C.M.; Canfield, A.E. Comparative quantification of the surfaceome of human multipotent mesenchymal progenitor cells. Stem Cell Reports, 2015, 4(3), 473-488.
[http://dx.doi.org/10.1016/j.stemcr.2015.01.007] [PMID: 25684225]

Zheng, H.; Liang, X.; Han, Q.; Shao, Z.; Zhang, Y.; Shi, L.; Hong, Y.; Li, W.; Mai, C.; Mo, Q.; Fu, Q.; Ma, X.; Lin, F.; Li, M.; Hu, B.; Li, X.; Zhang, Y. Hemin enhances the cardioprotective effects of mesenchymal stem cell-derived exosomes against infarction via amelioration of cardiomyocyte senescence. J. Nanobiotechnology, 2021, 19(1), 332.
[http://dx.doi.org/10.1186/s12951-021-01077-y] [PMID: 34674708]

Liang, B.; Liang, J.M.; Ding, J.N.; Xu, J.; Xu, J.G.; Chai, Y.M. Dimethyloxaloylglycine-stimulated human bone marrow mesenchymal stem cell-derived exosomes enhance bone regeneration through angiogenesis by targeting the AKT/mTOR pathway. Stem Cell Res. Ther., 2019, 10(1), 335.
[http://dx.doi.org/10.1186/s13287-019-1410-y] [PMID: 31747933]

Li, X.; Su, Z.; Shen, K.; Wang, Q.; Xu, C.; Wang, F.; Zhang, Y.; Jiang, D. Eugenol-preconditioned mesenchymal stem cell-derived extracellular vesicles promote antioxidant capacity of tendon stem cells in vitro and in vivo. Oxid. Med. Cell. Longev., 2022, 2022, 1-20.
[http://dx.doi.org/10.1155/2022/3945195] [PMID: 35178155]

Yu, M.; Liu, W.; Li, J.; Lu, J.; Lu, H.; Jia, W.; Liu, F. Exosomes derived from atorvastatin-pretreated MSC accelerate diabetic wound repair by enhancing angiogenesis via AKT/eNOS pathway. Stem Cell Res. Ther., 2020, 11(1), 350.
[http://dx.doi.org/10.1186/s13287-020-01824-2] [PMID: 32787917]

Huang, P.; Wang, L.; Li, Q.; Tian, X.; Xu, J.; Xu, J.; Xiong, Y.; Chen, G.; Qian, H.; Jin, C.; Yu, Y.; Cheng, K.; Qian, L.; Yang, Y. Atorvastatin enhances the therapeutic efficacy of mesenchymal stem cells-derived exosomes in acute myocardial infarction via up-regulating long non-coding RNA H19. Cardiovasc. Res., 2020, 116(2), 353-367.
[http://dx.doi.org/10.1093/cvr/cvz139] [PMID: 31119268]

Fu, M.; Xie, D.; Sun, Y.; Pan, Y.; Zhang, Y.; Chen, X.; Shi, Y.; Deng, S.; Cheng, B. Exosomes derived from MSC pre-treated with oridonin alleviates myocardial IR injury by suppressing apoptosis via regulating autophagy activation. J. Cell. Mol. Med., 2021, 25(12), 5486-5496.
[http://dx.doi.org/10.1111/jcmm.16558] [PMID: 33955654]

Hu, Y.; Tao, R.; Chen, L.; Xiong, Y.; Xue, H.; Hu, L.; Yan, C.; Xie, X.; Lin, Z.; Panayi, A.C.; Mi, B.; Liu, G. Exosomes derived from pioglitazone-pretreated MSCs accelerate diabetic wound healing through enhancing angiogenesis. J. Nanobiotechnology, 2021, 19(1), 150.
[http://dx.doi.org/10.1186/s12951-021-00894-5] [PMID: 34020670]

Calabrese, V.; Mancuso, C.; Calvani, M.; Rizzarelli, E.; Butterfield, D.A.; Giuffrida Stella, A.M. Nitric oxide in the central nervous system: Neuroprotection versus neurotoxicity. Nat. Rev. Neurosci., 2007, 8(10), 766-775.
[http://dx.doi.org/10.1038/nrn2214] [PMID: 17882254]

Yao, X.; Liu, Y.; Gao, J.; Yang, L.; Mao, D.; Stefanitsch, C.; Li, Y.; Zhang, J.; Ou, L.; Kong, D.; Zhao, Q.; Li, Z. Nitric oxide releasing hydrogel enhances the therapeutic efficacy of mesenchymal stem cells for myocardial infarction. Biomaterials, 2015, 60, 130-140.
[http://dx.doi.org/10.1016/j.biomaterials.2015.04.046] [PMID: 25988728]

Du, W.; Zhang, K.; Zhang, S.; Wang, R.; Nie, Y.; Tao, H.; Han, Z.; Liang, L.; Wang, D.; Liu, J.; Liu, N.; Han, Z.; Kong, D.; Zhao, Q.; Li, Z. Enhanced proangiogenic potential of mesenchymal stem cell-derived exosomes stimulated by a nitric oxide releasing polymer. Biomaterials, 2017, 133, 70-81.
[http://dx.doi.org/10.1016/j.biomaterials.2017.04.030] [PMID: 28433939]

Shelke, G.V.; Lässer, C.; Gho, Y.S.; Lötvall, J. Importance of exosome depletion protocols to eliminate functional and RNA-containing extracellular vesicles from fetal bovine serum. J. Extracell. Vesicles, 2014, 3(1), 24783.
[http://dx.doi.org/10.3402/jev.v3.24783] [PMID: 25317276]

Eitan, E.; Zhang, S.; Witwer, K.W.; Mattson, M.P. Extracellular vesicle–depleted fetal bovine and human sera have reduced capacity to support cell growth. J. Extracell. Vesicles, 2015, 4(1), 26373.
[http://dx.doi.org/10.3402/jev.v4.26373] [PMID: 25819213]

Lehrich, B.; Liang, Y.; Khosravi, P.; Federoff, H.; Fiandaca, M. Fetal bovine serum-derived extracellular vesicles persist within vesicle-depleted culture media. Int. J. Mol. Sci., 2018, 19(11), 3538.
[http://dx.doi.org/10.3390/ijms19113538] [PMID: 30423996]

Kornilov, R.; Puhka, M.; Mannerström, B.; Hiidenmaa, H.; Peltoniemi, H.; Siljander, P.; Seppänen-Kaijansinkko, R.; Kaur, S. Efficient ultrafiltration-based protocol to deplete extracellular vesicles from fetal bovine serum. J. Extracell. Vesicles, 2018, 7(1), 1422674.
[http://dx.doi.org/10.1080/20013078.2017.1422674] [PMID: 29410778]

Gerby, S.; Attebi, E.; Vlaski, M.; Ivanovic, Z. A new clinical-scale serum-free xeno-free medium efficient in ex vivo amplification of mesenchymal stromal cells does not support mesenchymal stem cells. Transfusion, 2017, 57(2), 433-439.
[http://dx.doi.org/10.1111/trf.13902] [PMID: 27861973]

Yoshida, K.; Nakashima, A.; Doi, S.; Ueno, T.; Okubo, T.; Kawano, K.; Kanawa, M.; Kato, Y.; Higashi, Y.; Masaki, T. Serum-free medium enhances the immunosuppressive and antifibrotic abilities of mesenchymal stem cells utilized in experimental renal fibrosis. Stem Cells Transl. Med., 2018, 7(12), 893-905.
[http://dx.doi.org/10.1002/sctm.17-0284] [PMID: 30269426]

Kim, J.Y.; Rhim, W.K.; Seo, H.J.; Lee, J.Y.; Park, C.G.; Han, D.K. Comparative analysis of MSC-derived exosomes depending on cell culture media for regenerative bioactivity. Tissue Eng. Regen. Med., 2021, 18(3), 355-367.
[http://dx.doi.org/10.1007/s13770-021-00352-1] [PMID: 34047999]

Figueroa-Valdés, A.I.; de la Fuente, C.; Hidalgo, Y.; Vega-Letter, A.M.; Tapia-Limonchi, R.; Khoury, M.; Alcayaga-Miranda, F. A chemically defined, xeno- and blood-free culture medium sustains increased production of small extracellular vesicles from mesenchymal stem cells. Front. Bioeng. Biotechnol., 2021, 9, 619930.
[http://dx.doi.org/10.3389/fbioe.2021.619930] [PMID: 34124014]

Haraszti, R.A.; Miller, R.; Dubuke, M.L.; Rockwell, H.E.; Coles, A.H.; Sapp, E.; Didiot, M.C.; Echeverria, D.; Stoppato, M.; Sere, Y.Y.; Leszyk, J.; Alterman, J.F.; Godinho, B.M.D.C.; Hassler, M.R.; McDaniel, J.; Narain, N.R.; Wollacott, R.; Wang, Y.; Shaffer, S.A.; Kiebish, M.A.; DiFiglia, M.; Aronin, N.; Khvorova, A. Serum deprivation of mesenchymal stem cells improves exosome activity and alters lipid and protein composition. iScience, 2019, 16, 230-241.
[http://dx.doi.org/10.1016/j.isci.2019.05.029] [PMID: 31195240]

Lehrich, B.M.; Liang, Y.; Fiandaca, M.S. Foetal bovine serum influence on in vitro extracellular vesicle analyses. J. Extracell. Vesicles, 2021, 10(3), e12061.
[http://dx.doi.org/10.1002/jev2.12061] [PMID: 33532042]

Xu, C.; Hou, L.; Zhao, J.; Wang, Y.; Jiang, F.; Jiang, Q.; Zhu, Z.; Tian, L. Exosomal let-7i-5p from three-dimensional cultured human umbilical cord mesenchymal stem cells inhibits fibroblast activation in silicosis through targeting TGFBR1. Ecotoxicol. Environ. Saf., 2022, 233, 113302.
[http://dx.doi.org/10.1016/j.ecoenv.2022.113302] [PMID: 35189518]

Su, N.; Gao, P.L.; Wang, K.; Wang, J.Y.; Zhong, Y.; Luo, Y. Fibrous scaffolds potentiate the paracrine function of mesenchymal stem cells: A new dimension in cell-material interaction. Biomaterials, 2017, 141, 74-85.
[http://dx.doi.org/10.1016/j.biomaterials.2017.06.028] [PMID: 28667901]

Huang, R.; Wang, J.; Chen, H.; Shi, X.; Wang, X.; Zhu, Y.; Tan, Z. The topography of fibrous scaffolds modulates the paracrine function of Ad-MSCs in the regeneration of skin tissues. Biomater. Sci., 2019, 7(10), 4248-4259.
[http://dx.doi.org/10.1039/C9BM00939F] [PMID: 31393466]

Yan, L.; Wu, X. Exosomes produced from 3D cultures of umbilical cord mesenchymal stem cells in a hollow-fiber bioreactor show improved osteochondral regeneration activity. Cell Biol. Toxicol., 2020, 36(2), 165-178.
[http://dx.doi.org/10.1007/s10565-019-09504-5] [PMID: 31820164]

Yang, L.; Zhai, Y.; Hao, Y.; Zhu, Z.; Cheng, G. The regulatory functionality of exosomes derived from humscs in 3d culture for alzheimer’s disease therapy. Small, 2020, 16(3), 1906273.
[http://dx.doi.org/10.1002/smll.201906273] [PMID: 31840420]

Cao, J.; Wang, B.; Tang, T.; Lv, L.; Ding, Z.; Li, Z.; Hu, R.; Wei, Q.; Shen, A.; Fu, Y.; Liu, B. Three-dimensional culture of MSCs produces exosomes with improved yield and enhanced therapeutic efficacy for cisplatin-induced acute kidney injury. Stem Cell Res. Ther., 2020, 11(1), 206.
[http://dx.doi.org/10.1186/s13287-020-01719-2] [PMID: 32460853]

Yu, W.; Li, S.; Guan, X.; Zhang, N.; Xie, X.; Zhang, K.; Bai, Y. Higher yield and enhanced therapeutic effects of exosomes derived from MSCs in hydrogel-assisted 3D culture system for bone regeneration. Biomaterials Advances, 2022, 133, 112646.
[http://dx.doi.org/10.1016/j.msec.2022.112646] [PMID: 35067433]

Kim, M.; Yun, H.W.; Park, D.Y.; Choi, B.H.; Min, B.H. Three-dimensional spheroid culture increases exosome secretion from mesenchymal stem cells. Tissue Eng. Regen. Med., 2018, 15(4), 427-436.
[http://dx.doi.org/10.1007/s13770-018-0139-5] [PMID: 30603566]

Zhang, Y.; Chen, J.; Fu, H.; Kuang, S.; He, F.; Zhang, M.; Shen, Z.; Qin, W.; Lin, Z.; Huang, S. Exosomes derived from 3D-cultured MSCs improve therapeutic effects in periodontitis and experimental colitis and restore the Th17 cell/Treg balance in inflamed periodontium. Int. J. Oral Sci., 2021, 13(1), 43.
[http://dx.doi.org/10.1038/s41368-021-00150-4] [PMID: 34907166]

Haraszti, R.A.; Miller, R.; Stoppato, M.; Sere, Y.Y.; Coles, A.; Didiot, M.C.; Wollacott, R.; Sapp, E.; Dubuke, M.L.; Li, X.; Shaffer, S.A.; DiFiglia, M.; Wang, Y.; Aronin, N.; Khvorova, A. Exosomes Produced from 3D Cultures of MSCs by Tangential Flow Filtration Show Higher Yield and Improved Activity. Mol. Ther., 2018, 26(12), 2838-2847.
[http://dx.doi.org/10.1016/j.ymthe.2018.09.015] [PMID: 30341012]

Wang, N.; Li, X.; Zhong, Z.; Qiu, Y.; Liu, S.; Wu, H.; Tang, X.; Chen, C.; Fu, Y.; Chen, Q.; Guo, T.; Li, J.; Zhang, S.; Zern, M.A.; Ma, K.; Wang, B.; Ou, Y.; Gu, W.; Cao, J.; Chen, H.; Duan, Y. 3D hESC exosomes enriched with miR-6766-3p ameliorates liver fibrosis by attenuating activated stellate cells through targeting the TGFβRII-SMADS pathway. J. Nanobiotechnology, 2021, 19(1), 437.
[http://dx.doi.org/10.1186/s12951-021-01138-2] [PMID: 34930304]

Liu, L.; Liu, Y.; Feng, C.; Chang, J.; Fu, R.; Wu, T.; Yu, F.; Wang, X.; Xia, L.; Wu, C.; Fang, B. Lithium-containing biomaterials stimulate bone marrow stromal cell-derived exosomal miR-130a secretion to promote angiogenesis. Biomaterials, 2019, 192, 523-536.
[http://dx.doi.org/10.1016/j.biomaterials.2018.11.007] [PMID: 30529871]

Wasupalli, G.K.; Verma, D. Injectable and thermosensitive nanofibrous hydrogel for bone tissue engineering. Mater. Sci. Eng. C, 2020, 107, 110343.
[http://dx.doi.org/10.1016/j.msec.2019.110343] [PMID: 31761212]

Sun, J.; Mou, C.; Shi, Q.; Chen, B.; Hou, X.; Zhang, W.; Li, X.; Zhuang, Y.; Shi, J.; Chen, Y.; Dai, J. Controlled release of collagen-binding SDF-1α from the collagen scaffold promoted tendon regeneration in a rat Achilles tendon defect model. Biomaterials, 2018, 162, 22-33.
[http://dx.doi.org/10.1016/j.biomaterials.2018.02.008] [PMID: 29428676]

Liu, Y.; Cui, J.; Wang, H.; Hezam, K.; Zhao, X.; Huang, H.; Chen, S.; Han, Z.; Han, Z.C.; Guo, Z.; Li, Z. Enhanced therapeutic effects of MSC-derived extracellular vesicles with an injectable collagen matrix for experimental acute kidney injury treatment. Stem Cell Res. Ther., 2020, 11(1), 161.
[http://dx.doi.org/10.1186/s13287-020-01668-w] [PMID: 32321594]

Wu, Z.; He, D.; Li, H. Bioglass enhances the production of exosomes and improves their capability of promoting vascularization. Bioact. Mater., 2021, 6(3), 823-835.
[http://dx.doi.org/10.1016/j.bioactmat.2020.09.011] [PMID: 33024902]

Gardin, C.; Ferroni, L. Erdoğan, Y.K.; Zanotti, F.; De Francesco, F.; Trentini, M.; Brunello, G.; Ercan, B.; Zavan, B. Nanostructured modifications of titanium surfaces improve vascular regenerative properties of exosomes derived from mesenchymal stem cells: preliminary in vitro results. Nanomaterials (Basel), 2021, 11(12), 3452.
[http://dx.doi.org/10.3390/nano11123452] [PMID: 34947800]

Park, D.J.; Yun, W.S.; Kim, W.C.; Park, J.E.; Lee, S.H.; Ha, S.; Choi, J.S.; Key, J.; Seo, Y.J. Improvement of stem cell-derived exosome release efficiency by surface-modified nanoparticles. J. Nanobiotechnology, 2020, 18(1), 178.
[http://dx.doi.org/10.1186/s12951-020-00739-7] [PMID: 33287848]

Gurunathan, S.; Kang, M.H.; Jeyaraj, M.; Kim, J.H. Palladium nanoparticle-induced oxidative stress, endoplasmic reticulum stress, apoptosis, and immunomodulation enhance the biogenesis and release of exosome in human leukemia monocytic cells (THP-1). Int. J. Nanomedicine, 2021, 16, 2849-2877.
[http://dx.doi.org/10.2147/IJN.S305269] [PMID: 33883895]

Gurunathan, S.; Kang, M.H.; Jeyaraj, M.; Kim, J.H. Platinum nanoparticles enhance exosome release in human lung epithelial adenocarcinoma cancer cells (A549): Oxidative stress and the ceramide pathway are key players. Int. J. Nanomedicine, 2021, 16, 515-538.
[http://dx.doi.org/10.2147/IJN.S291138] [PMID: 33519199]

Álvarez-Viejo, M. Mesenchymal stem cells from different sources and their derived exosomes: A pre-clinical perspective. World J. Stem Cells, 2020, 12(2), 100-109.
[http://dx.doi.org/10.4252/wjsc.v12.i2.100] [PMID: 32184935]

Hass, R.; Kasper, C.; Böhm, S.; Jacobs, R. Different populations and sources of human mesenchymal stem cells (MSC): A comparison of adult and neonatal tissue-derived MSC. Cell Commun. Signal., 2011, 9(1), 12.
[http://dx.doi.org/10.1186/1478-811X-9-12] [PMID: 21569606]

Tracy, S.A.; Ahmed, A.; Tigges, J.C.; Ericsson, M.; Pal, A.K.; Zurakowski, D.; Fauza, D.O. A comparison of clinically relevant sources of mesenchymal stem cell-derived exosomes: Bone marrow and amniotic fluid. J. Pediatr. Surg., 2019, 54(1), 86-90.
[http://dx.doi.org/10.1016/j.jpedsurg.2018.10.020] [PMID: 30361074]

Ji, L.; Bao, L.; Gu, Z.; Zhou, Q.; Liang, Y.; Zheng, Y.; Xu, Y.; Zhang, X.; Feng, X. Comparison of immunomodulatory properties of exosomes derived from bone marrow mesenchymal stem cells and dental pulp stem cells. Immunol. Res., 2019, 67(4-5), 432-442.
[http://dx.doi.org/10.1007/s12026-019-09088-6] [PMID: 31407157]

Liao, Q.; Li, B.J.; Li, Y.; Xiao, Y.; Zeng, H.; Liu, J.M.; Yuan, L.X.; Liu, G. Low-intensity pulsed ultrasound promotes osteoarthritic cartilage regeneration by BMSC-derived exosomes via modulating the NF-κB signaling pathway. Int. Immunopharmacol., 2021, 97, 107824.
[http://dx.doi.org/10.1016/j.intimp.2021.107824] [PMID: 34102487]

Snehota, M.; Vachutka, J.; ter Haar, G.; Dolezal, L.; Kolarova, H. Therapeutic ultrasound experiments in vitro: Review of factors influencing outcomes and reproducibility. Ultrasonics, 2020, 107, 106167.
[http://dx.doi.org/10.1016/j.ultras.2020.106167] [PMID: 32402858]

Bai, Y.; Han, Y.; Yan, X.; Ren, J.; Zeng, Q.; Li, X.; Pei, X.; Han, Y. Adipose mesenchymal stem cell-derived exosomes stimulated by hydrogen peroxide enhanced skin flap recovery in ischemia-reperfusion injury. Biochem. Biophys. Res. Commun., 2018, 500(2), 310-317.
[http://dx.doi.org/10.1016/j.bbrc.2018.04.065] [PMID: 29654765]

Stojiljković A.; Gaschen, V.; Forterre, F.; Rytz, U.; Stoffel, M.H.; Bluteau, J. Novel immortalization approach defers senescence of cultured canine adipose-derived mesenchymal stromal cells. Geroscience, 2022, 44(3), 1301-1323.
[PMID: 34806133]

Lai, R.C.; Yeo, R.W.Y.; Padmanabhan, J.; Choo, A.; de Kleijn, D.P.V.; Lim, S.K. Isolation and Characterization of Exosome from Human Embryonic Stem Cell-Derived C-Myc-Immortalized Mesenchymal Stem Cells. Methods Mol. Biol., 2016, 1416, 477-494.
[http://dx.doi.org/10.1007/978-1-4939-3584-0_29] [PMID: 27236691]

Yang, Z.; Shi, J.; Xie, J.; Wang, Y.; Sun, J.; Liu, T.; Zhao, Y.; Zhao, X.; Wang, X.; Ma, Y.; Malkoc, V.; Chiang, C.; Deng, W.; Chen, Y.; Fu, Y.; Kwak, K.J.; Fan, Y.; Kang, C.; Yin, C.; Rhee, J.; Bertani, P.; Otero, J.; Lu, W.; Yun, K.; Lee, A.S.; Jiang, W.; Teng, L.; Kim, B.Y.S.; Lee, L.J. Large-scale generation of functional mRNA-encapsulating exosomes via cellular nanoporation. Nat. Biomed. Eng., 2020, 4(1), 69-83.
[http://dx.doi.org/10.1038/s41551-019-0485-1] [PMID: 31844155]

Kimiz-Gebologlu, I.; Oncel, S.S. Exosomes: Large-scale production, isolation, drug loading efficiency, and biodistribution and uptake. J. Control. Release, 2022, 347, 533-543.
[http://dx.doi.org/10.1016/j.jconrel.2022.05.027] [PMID: 35597405]

Lee, J.H.; Ha, D.H.; Go, H.; Youn, J.; Kim, H.; Jin, R.C.; Miller, R.B.; Kim, D.; Cho, B.S.; Yi, Y.W. Reproducible large-scale isolation of exosomes from adipose tissue-derived mesenchymal stem/stromal cells and their application in acute kidney injury. Int. J. Mol. Sci., 2020, 21(13), 4774.
[http://dx.doi.org/10.3390/ijms21134774] [PMID: 32635660]

Burnouf, T.; Strunk, D.; Koh, M.B.C.; Schallmoser, K. Human platelet lysate: Replacing fetal bovine serum as a gold standard for human cell propagation? Biomaterials, 2016, 76, 371-387.
[http://dx.doi.org/10.1016/j.biomaterials.2015.10.065] [PMID: 26561934]

Pachler, K.; Lener, T.; Streif, D.; Dunai, Z.A.; Desgeorges, A.; Feichtner, M.; Öller, M.; Schallmoser, K.; Rohde, E.; Gimona, M. A Good Manufacturing Practice–grade standard protocol for exclusively human mesenchymal stromal cell–derived extracellular vesicles. Cytotherapy, 2017, 19(4), 458-472.
[http://dx.doi.org/10.1016/j.jcyt.2017.01.001] [PMID: 28188071]

Andriolo, G.; Provasi, E.; Lo Cicero, V.; Brambilla, A.; Soncin, S.; Torre, T.; Milano, G.; Biemmi, V.; Vassalli, G.; Turchetto, L.; Barile, L.; Radrizzani, M. Exosomes from human cardiac progenitor cells for therapeutic applications: Development of a GMP-grade manufacturing method. Front. Physiol., 2018, 9, 1169.
[http://dx.doi.org/10.3389/fphys.2018.01169] [PMID: 30197601]

Mendt, M.; Kamerkar, S.; Sugimoto, H.; McAndrews, K.M.; Wu, C.C.; Gagea, M.; Yang, S.; Blanko, E.V.R.; Peng, Q.; Ma, X.; Marszalek, J.R.; Maitra, A.; Yee, C.; Rezvani, K.; Shpall, E.; LeBleu, V.S.; Kalluri, R. Generation and testing of clinical-grade exosomes for pancreatic cancer. JCI Insight, 2018, 3(8), e99263.
[http://dx.doi.org/10.1172/jci.insight.99263] [PMID: 29669940]

Syromiatnikova, V.; Prokopeva, A.; Gomzikova, M. Methods of the large-scale production of extracellular vesicles. Int. J. Mol. Sci., 2022, 23(18), 10522.
[http://dx.doi.org/10.3390/ijms231810522] [PMID: 36142433]

Corso, G.; Mäger, I.; Lee, Y.; Görgens, A.; Bultema, J.; Giebel, B.; Wood, M.J.A.; Nordin, J.Z.; Andaloussi, S.E.L. Reproducible and scalable purification of extracellular vesicles using combined bind-elute and size exclusion chromatography. Sci. Rep., 2017, 7(1), 11561.
[http://dx.doi.org/10.1038/s41598-017-10646-x] [PMID: 28912498]

Royo, F.; Théry, C.; Falcón-Pérez, J.M.; Nieuwland, R.; Witwer, K.W. Methods for separation and characterization of extracellular vesicles: Results of a worldwide survey performed by the ISEV Rigor and standardization subcommittee. Cells, 2020, 9(9), 1955.
[http://dx.doi.org/10.3390/cells9091955] [PMID: 32854228]

Liangsupree, T.; Multia, E.; Riekkola, M.L. Modern isolation and separation techniques for extracellular vesicles. J. Chromatogr. A, 2021, 1636, 461773.
[http://dx.doi.org/10.1016/j.chroma.2020.461773] [PMID: 33316564]

Visan, K.S.; Lobb, R.J.; Ham, S.; Lima, L.G.; Palma, C.; Edna, C.P.Z.; Wu, L.Y.; Gowda, H.; Datta, K.K.; Hartel, G.; Salomon, C.; Möller, A. Comparative analysis of tangential flow filtration and ultracentrifugation, both combined with subsequent size exclusion chromatography, for the isolation of small extracellular vesicles. J. Extracell. Vesicles, 2022, 11(9), 12266.
[http://dx.doi.org/10.1002/jev2.12266] [PMID: 36124834]

Chernyshev, V.S.; Chuprov-Netochin, R.N.; Tsydenzhapova, E.; Svirshchevskaya, E.V.; Poltavtseva, R.A.; Merdalimova, A.; Yashchenok, A.; Keshelava, A.; Sorokin, K.; Keshelava, V.; Sukhikh, G.T.; Gorin, D.; Leonov, S.; Skliar, M. Asymmetric depth-filtration: A versatile and scalable method for high-yield isolation of extracellular vesicles with low contamination. J. Extracell. Vesicles, 2022, 11(8), e12256.
[http://dx.doi.org/10.1002/jev2.12256] [PMID: 35942823]

Anusha, R.; Priya, S. Dietary exosome-like nanoparticles: An updated review on their pharmacological and drug delivery applications. Mol. Nutr. Food Res., 2022, 66(14), 2200142.
[http://dx.doi.org/10.1002/mnfr.202200142] [PMID: 35593481]

Subudhi, P.D.; Bihari, C.; Sarin, S.K.; Baweja, S. Emerging role of edible exosomes-like nanoparticles (ELNs) as hepatoprotective agents. Nanotheranostics, 2022, 6(4), 365-375.
[http://dx.doi.org/10.7150/ntno.70999] [PMID: 35795340]

Lei, C.; Mu, J.; Teng, Y.; He, L.; Xu, F.; Zhang, X.; Sundaram, K.; Kumar, A.; Sriwastva, M.K.; Lawrenz, M.B.; Zhang, L.; Yan, J.; Feng, W.; McClain, C.J.; Zhang, X.; Zhang, H.G. Lemon Exosome-like Nanoparticles-Manipulated Probiotics Protect Mice from C. diff Infection. iScience, 2020, 23(10), 101571.
[http://dx.doi.org/10.1016/j.isci.2020.101571] [PMID: 33083738]

Wang, B.; Zhuang, X.; Deng, Z.B.; Jiang, H.; Mu, J.; Wang, Q.; Xiang, X.; Guo, H.; Zhang, L.; Dryden, G.; Yan, J.; Miller, D.; Zhang, H.G. Targeted drug delivery to intestinal macrophages by bioactive nanovesicles released from grapefruit. Mol. Ther., 2014, 22(3), 522-534.
[http://dx.doi.org/10.1038/mt.2013.190] [PMID: 23939022]

Dad, H.A.; Gu, T.W.; Zhu, A.Q.; Huang, L.Q.; Peng, L.H. Plant exosome-like nanovesicles: Emerging therapeutics and drug delivery nanoplatforms. Mol. Ther., 2021, 29(1), 13-31.
[http://dx.doi.org/10.1016/j.ymthe.2020.11.030] [PMID: 33278566]

Zhang, M.; Viennois, E.; Prasad, M.; Zhang, Y.; Wang, L.; Zhang, Z.; Han, M.K.; Xiao, B.; Xu, C.; Srinivasan, S.; Merlin, D. Edible ginger-derived nanoparticles: A novel therapeutic approach for the prevention and treatment of inflammatory bowel disease and colitis-associated cancer. Biomaterials, 2016, 101, 321-340.
[http://dx.doi.org/10.1016/j.biomaterials.2016.06.018] [PMID: 27318094]

Zhuang, X.; Deng, Z.B.; Mu, J.; Zhang, L.; Yan, J.; Miller, D.; Feng, W.; McClain, C.J.; Zhang, H.G. Ginger-derived nanoparticles protect against alcohol-induced liver damage. J. Extracell. Vesicles, 2015, 4(1), 28713.
[http://dx.doi.org/10.3402/jev.v4.28713] [PMID: 26610593]

Drake, J.; Sultana, R.; Aksenova, M.; Calabrese, V.; Butterfield, D.A. Elevation of mitochondrial glutathione by? -glutamylcysteine ethyl ester protects mitochondria against peroxynitrite-induced oxidative stress. J. Neurosci. Res., 2003, 74(6), 917-927.
[http://dx.doi.org/10.1002/jnr.10810] [PMID: 14648597]

Chen, Q.; Li, Q.; Liang, Y.; Zu, M.; Chen, N.; Canup, B.S.B.; Luo, L.; Wang, C.; Zeng, L.; Xiao, B. Natural exosome-like nanovesicles from edible tea flowers suppress metastatic breast cancer via ROS generation and microbiota modulation. Acta Pharm. Sin. B, 2022, 12(2), 907-923.
[http://dx.doi.org/10.1016/j.apsb.2021.08.016] [PMID: 35256954]