Engineering of Extracellular Vesicles Based on Payload Changes for Tissue Regeneration

Abstract

In the field of tissue regeneration and tissue engineering, many years ago, various nano to macroscopic-sized materials have been used to reduce inflammation and restore damaged tissue. Whether it is safe to study the regeneration of all tissues based on the biological mechanisms of an organism composed of cells is still debated, and studies using extracellular vesicles derived from cells have become popular in the past decade. It has been reported that exosomes with a size of 100 nm or less, which plays an important role in cell–cell communication, contain various factors, such as proliferation, anti-inflammatory, and growth factors. In addition, the payload of exosomes varies depending on the parent cell and the recipient cell, and a technology to differentiate the selective payload must treat specific diseases. In this review, we examined the current trends in research using exosomes derived from cells or tissues and analyzed various research reports on factors that can affect tissue regeneration.

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References

  1. 1.

    Maas SLN, Breakefield XO, Weaver AM. Extracellular vesicles: unique intercellular delivery vehicles. Trends Cell Biol. 2017;27:172–88.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  2. 2.

    Danzer KM, Kranich LR, Ruf WP, Cagsal-Getkin O, Winslow AR, Zhu L, et al. Exosomal cell-to-cell transmission of alpha synuclein oligomers. Mol Neurodegener. 2012;7:42.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  3. 3.

    Lázaro-Ibáñez E, Sanz-Garcia A, Visakorpi T, Escobedo-Lucea C, Siljander P, Ayuso-Sacido A, et al. Different gDNA content in the subpopulations of prostate cancer extracellular vesicles: apoptotic bodies, microvesicles, and exosomes. Prostate. 2014;74:1379–90.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  4. 4.

    Thakur BK, Zhang H, Becker A, Matei I, Huang Y, Costa-Silva B, et al. Double-stranded DNA in exosomes: a novel biomarker in cancer detection. Cell Res. 2014;24:766–9.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  5. 5.

    Jeppesen DK, Fenix AM, Franklin JL, Higginbotham JN, Zhang Q, Zimmerman LJ, et al. Reassessment of exosome composition. Cell. 2019;177:428–45.e18.

    Article  CAS  Google Scholar 

  6. 6.

    Kalluri R, LeBleu VS. The biology, function, and biomedical applications of exosomes. Science. 2020;367:eaau6977.

  7. 7.

    Jackson CE, Scruggs BS, Schaffer JE, Hanson PI. Effects of inhibiting VPS4 support a general role for ESCRTs in extracellular vesicle biogenesis. Biophys J. 2017;113:1342–52.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  8. 8.

    Colombo M, Moita C, van Niel G, Kowal J, Vigneron J, Benaroch P, et al. Analysis of ESCRT functions in exosome biogenesis, composition and secretion highlights the heterogeneity of extracellular vesicles. J Cell Sci. 2013;126:5553–65.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. 9.

    Joshi BS, de Beer MA, Giepmans BG, Zuhorn IS. Endocytosis of extracellular vesicles and release of their cargo from endosomes. ACS Nano. 2020;14:4444–55.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  10. 10.

    Buratta S, Tancini B, Sagini K, Delo F, Chiaradia E, Urbanelli L, et al. Lysosomal exocytosis, exosome release and secretory autophagy: the autophagic- and endo-lysosomal systems go extracellular. Int J Mol Sci. 2020;21:2576.

    CAS  PubMed Central  Article  Google Scholar 

  11. 11.

    Pisano S, Pierini I, Gu J, Gazze A, Francis LW, Gonzalez D, et al. Immune (cell) derived exosome mimetics (IDEM) as a treatment for ovarian cancer. Front Cell Dev Biol. 2020;8:553576.

    PubMed  PubMed Central  Article  Google Scholar 

  12. 12.

    Zhou X, Xie F, Wang L, Zhang L, Zhang S, Fang M, et al. The function and clinical application of extracellular vesicles in innate immune regulation. Cell Mol Immunol. 2020;17:323–34.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  13. 13.

    Cho BS, Kim JO, Ha DH, Yi YW. Exosomes derived from human adipose tissue-derived mesenchymal stem cells alleviate atopic dermatitis. Stem Cell Res Ther. 2018;9:187.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  14. 14.

    Xu K, Zhang C, Du T, Gabriel ANA, Wang X, Li X, et al. Progress of exosomes in the diagnosis and treatment of lung cancer. Biomed Pharmacother. 2021;134:111111.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  15. 15.

    Prikryl P, Satrapova V, Frydlova J, Hruskova Z, Zima T, Tesar V, et al. Mass spectrometry-based proteomic exploration of the small urinary extracellular vesicles in ANCA-associated vasculitis in comparison with total urine. J Proteomics. 2021;233:104067.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  16. 16.

    Shenoy GN, Bhatta M, Loyall JL, Kelleher RJ Jr, Bernstein JM, Bankert RB. Exosomes represent an immune suppressive T cell checkpoint in human chronic inflammatory microenvironments. Immunol Invest. 2020;49:726–43.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  17. 17.

    Poggio M, Hu T, Pai CC, Chu B, Belair CD, Chang A, et al. Suppression of exosomal PD-L1 induces systemic anti-tumor immunity and memory. Cell. 2019;177:414–27.e13.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  18. 18.

    Chen G, Huang AC, Zhang W, Zhang G, Wu M, Xu W, et al. Exosomal PD-L1 contributes to immunosuppression and is associated with anti-PD-1 response. Nature. 2018;560:382–6.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  19. 19.

    Wan Z, Gao X, Dong Y, Zhao Y, Chen X, Yang G, et al. Exosome-mediated cell-cell communication in tumor progression. Am J Cancer Res. 2018;8:1661–73.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. 20.

    Cho KHT, Xu B, Blenkiron C, Fraser M. Emerging roles of miRNAs in brain development and perinatal brain injury. Front Physiol. 2019;10:227.

    PubMed  PubMed Central  Article  Google Scholar 

  21. 21.

    Yi X, Wei X, Lv H, An Y, Li L, Lu P, et al. Exosomes derived from microRNA-30b-3p-overexpressing mesenchymal stem cells protect against lipopolysaccharide-induced acute lung injury by inhibiting SAA3. Exp Cell Res. 2019;383:111454.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  22. 22.

    Scott CC, Vacca F, Gruenberg J. Endosome maturation, transport and functions. Semin Cell Dev Biol. 2014;31:2–10.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  23. 23.

    Xia L, Gu W, Zhang M, Chang YN, Chen K, Bai X, et al. Endocytosed nanoparticles hold endosomes and stimulate binucleated cells formation. Part Fibre Toxicol. 2016;13:63.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  24. 24.

    Woodman PG, Futter CE. Multivesicular bodies: co-ordinated progression to maturity. Curr Opin Cell Biol. 2008;20:408–14.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  25. 25.

    Trajkovic K, Hsu C, Chiantia S, Rajendran L, Wenzel D, Wieland F, et al. Ceramide triggers budding of exosome vesicles into multivesicular endosomes. Science. 2008;319:1244–7.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  26. 26.

    Keerthikumar S, Gangoda L, Liem M, Fonseka P, Atukorala I, Ozcitti C, et al. Proteogenomic analysis reveals exosomes are more oncogenic than ectosomes. Oncotarget. 2015;6:15375–96.

    PubMed  PubMed Central  Article  Google Scholar 

  27. 27.

    Hurley JH, Odorizzi G. Get on the exosome bus with ALIX. Nat Cell Biol. 2012;14:654–5.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  28. 28.

    Perez-Hernandez D, Gutiérrez-Vázquez C, Jorge I, López-Martín S, Ursa A, Sánchez-Madrid F, et al. The intracellular interactome of tetraspanin-enriched microdomains reveals their function as sorting machineries toward exosomes. J Biol Chem. 2013;288:11649–61.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  29. 29.

    Moreno-Gonzalo O, Fernandez-Delgado I, Sanchez-Madrid F. Post-translational add-ons mark the path in exosomal protein sorting. Cell Mol Life Sci. 2018;75:1–19.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  30. 30.

    Kahlert C, Melo SA, Protopopov A, Tang J, Seth S, Koch M, et al. Identification of double-stranded genomic DNA spanning all chromosomes with mutated KRAS and p53 DNA in the serum exosomes of patients with pancreatic cancer. J Biol Chem. 2014;289:3869–75.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  31. 31.

    Cai J, Wu G, Jose PA, Zeng C. Functional transferred DNA within extracellular vesicles. Exp Cell Res. 2016;349:179–83.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  32. 32.

    Guescini M, Genedani S, Stocchi V, Agnati LF. Astrocytes and Glioblastoma cells release exosomes carrying mtDNA. J Neural Transm (Vienna). 2010;117:1–4.

    CAS  Article  Google Scholar 

  33. 33.

    Bolukbasi MF, Mizrak A, Ozdener GB, Madlener S, Ströbel T, Erkan EP, et al. miR-1289 and “zipcode”-like sequence enrich mRNAs in microvesicles. Mol Ther Nucleic Acids. 2012;1:e10.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  34. 34.

    Kulkarni B, Gondaliya P, Kirave P, Rawal R, Jain A, Garg R, et al. Exosome-mediated delivery of miR-30a sensitize cisplatin-resistant variant of oral squamous carcinoma cells via modulating Beclin1 and Bcl2. Oncotarget. 2020;11:1832–45.

    PubMed  PubMed Central  Article  Google Scholar 

  35. 35.

    Gidlöf O, Evander M, Rezeli M, Marko-Varga G, Laurell T, Erlinge D. Proteomic profiling of extracellular vesicles reveals additional diagnostic biomarkers for myocardial infarction compared to plasma alone. Sci Rep. 2019;9:8991.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  36. 36.

    Huang G, Lin G, Zhu Y, Duan W, Jin D. Emerging technologies for profiling extracellular vesicle heterogeneity. Lab Chip. 2020;20:2423–37.

    CAS  PubMed  Article  Google Scholar 

  37. 37.

    Wortzel I, Dror S, Kenific CM, Lyden D. Exosome-mediated metastasis: communication from a distance. Dev Cell. 2019;49:347–60.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  38. 38.

    Garcia-Romero N, Esteban-Rubio S, Rackov G, Carrión-Navarro J, Belda-Iniesta C, Ayuso-Sacido A. Extracellular vesicles compartment in liquid biopsies: clinical application. Mol Aspects Med. 2018;60:27–37.

    CAS  PubMed  Article  Google Scholar 

  39. 39.

    Delpech JC, Herron S, Botros MB, Ikezu T. Neuroimmune crosstalk through extracellular vesicles in health and disease. Trends Neurosci. 2019;42:361–72.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  40. 40.

    Raimondo S, Giavaresi G, Lorico A, Alessandro R. Extracellular vesicles as biological shuttles for targeted therapies. Int J Mol Sci. 2019;20:1848.

    CAS  PubMed Central  Article  Google Scholar 

  41. 41.

    Antes TJ, Middleton RC, Luther KM, Ijichi T, Peck KA, Liu WJ, et al. Targeting extracellular vesicles to injured tissue using membrane cloaking and surface display. J Nanobiotechnology. 2018;16:61.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  42. 42.

    Quiroz-Baez R, Hernández-Ortega K, Martínez-Martínez E. Insights into the proteomic profiling of extracellular vesicles for the identification of early biomarkers of neurodegeneration. Front Neurol. 2020;11:580030.

    PubMed  PubMed Central  Article  Google Scholar 

  43. 43.

    Nelson BC, Maragh S, Ghiran IC, Jones JC, DeRose PC, Elsheikh E, et al. Measurement and standardization challenges for extracellular vesicle therapeutic delivery vectors. Nanomedicine (Lond). 2020;15:2149–70.

    CAS  Article  Google Scholar 

  44. 44.

    Gonda A, Kabagwira J, Senthil GN, Wall NR. Internalization of exosomes through receptor-mediated endocytosis. Mol Cancer Res. 2019;17:337–47.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  45. 45.

    Mathieu M, Martin-Jaular L, Lavieu G, Thery C. Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell-to-cell communication. Nat Cell Biol. 2019;21:9–17.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  46. 46.

    Tintut Y, Demer LL. Exosomes: nanosized cellular messages. Circ Res. 2015;116:1281–3.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  47. 47.

    Tkach M, Théry C. Communication by extracellular vesicles: where we are and where we need to go. Cell. 2016;164:1226–32.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  48. 48.

    Morrissey SM, Yan J. Exosomal PD-L1: roles in tumor progression and immunotherapy. Trends Cancer. 2020;6:550–8.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  49. 49.

    Lopez-Verrilli MA, Court FA. Exosomes: mediators of communication in eukaryotes. Biol Res. 2013;46:5–11.

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  50. 50.

    Gutiérrez-Vázquez C, Villarroya-Beltri C, Mittelbrunn M, Sánchez-Madrid F. Transfer of extracellular vesicles during immune cell–cell interactions. Immunol Rev. 2013;251:125–42.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  51. 51.

    Harding CV, Heuser JE, Stahl PD. Exosomes: looking back three decades and into the future. J Cell Biol. 2013;200:367–71.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  52. 52.

    Bianco NR, Kim SH, Morelli AE, Robbins PD. Modulation of the immune response using dendritic cell-derived exosomes. Methods Mol Biol. 2007;380:443–55.

  53. 53.

    Zhou Y, Zhou W, Chen X, Wang Q, Li C, Chen Q, et al. Bone marrow mesenchymal stem cells-derived exosomes for penetrating and targeted chemotherapy of pancreatic cancer. Acta Pharm Sin B. 2020;10:1563–75.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  54. 54.

    Qin S, Dorschner RA, Masini I, Lavoie-Gagne O, Stahl PD, Costantini TW, et al. TBC1D3 regulates the payload and biological activity of extracellular vesicles that mediate tissue repair. FASEB J. 2019;33:6129–39.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  55. 55.

    Beauvillain C, Ruiz S, Guiton R, Bout D, Dimier-Poisson I. A vaccine based on exosomes secreted by a dendritic cell line confers protection against T. gondii infection in syngeneic and allogeneic mice. Microbes Infect. 2007;9:1614–22.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  56. 56.

    Giri PK, Schorey JS. Exosomes derived from M. Bovis BCG infected macrophages activate antigen-specific CD4+ and CD8+ T cells in vitro and in vivo. PLoS One. 2008;3:e2461.

  57. 57.

    Keryer-Bibens C, Pioche-Durieu C, Villemant C, Souquère S, Nishi N, Hirashima M, et al. Exosomes released by EBV-infected nasopharyngeal carcinoma cells convey the viral latent membrane protein 1 and the immunomodulatory protein galectin 9. BMC Cancer. 2006;6:283.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  58. 58.

    Zhou X, Brown BA, Siegel AP, El Masry MS, Zeng X, Song W, et al. Exosome-mediated crosstalk between keratinocytes and macrophages in cutaneous wound healing. ACS Nano. 2020;14:12732–48.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  59. 59.

    Shin KO, Ha DH, Kim JO, Crumrine DA, Meyer JM, Wakefield JS, et al. Exosomes from human adipose tissue-derived mesenchymal stem cells promote epidermal barrier repair by inducing de novo synthesis of ceramides in atopic dermatitis. Cells. 2020;9:680.

    CAS  PubMed Central  Article  Google Scholar 

  60. 60.

    From the American Association of Neurological Surgeons, American Society of Neuroradiology, Cardiovascular Interventional Radiology Society of Europe, Canadian Interventional Radiology Association, Congress of Neurological Surgeons, European Society of Minimally Invasive Neurological Therapy, et al. Multisociety consensus quality improvement revised consensus statement for endovascular therapy of acute ischemic stroke. Int J Stroke. 2018;13:612–32.

  61. 61.

    Hashimoto H, Olson EN, Bassel-Duby R. Therapeutic approaches for cardiac regeneration and repair. Nat Rev Cardiol. 2018;15:585–600.

    PubMed  PubMed Central  Article  Google Scholar 

  62. 62.

    Bellin G, Gardin C, Ferroni L, Chachques JC, Rogante M, Mitrečić D, et al. Exosome in cardiovascular diseases: a complex world full of hope. Cells. 2019;8:166.

    CAS  PubMed Central  Article  Google Scholar 

  63. 63.

    Lin Y, Anderson JD, Rahnama LMA, Gu SV, Knowlton AA. Exosomes in disease and regeneration: biological functions, diagnostics, and beneficial effects. Am J Physiol Heart Circ Physiol. 2020;319:H1162–80.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  64. 64.

    Gallet R, Dawkins J, Valle J, Simsolo E, de Couto G, Middleton R, et al. 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;38:201–11.

    CAS  PubMed  PubMed Central  Google Scholar 

  65. 65.

    Baruah J, Wary KK. Exosomes in the regulation of vascular endothelial cell regeneration. Front Cell Dev Biol. 2020;7:353.

    PubMed  PubMed Central  Article  Google Scholar 

  66. 66.

    Barile L, Lionetti V, Cervio E, Matteucci M, Gherghiceanu M, Popescu LM, et al. Extracellular vesicles from human cardiac progenitor cells inhibit cardiomyocyte apoptosis and improve cardiac function after myocardial infarction. Cardiovasc Res. 2014;103:530–41.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  67. 67.

    Ibrahim AGE, Cheng K, Marban E. Exosomes as critical agents of cardiac regeneration triggered by cell therapy. Stem Cell Rep. 2014;2:606–19.

    CAS  Article  Google Scholar 

  68. 68.

    Qu Y, Zhang Q, Cai X, Li F, Ma Z, Xu M, et al. Exosomes derived from miR-181-5p-modified adipose-derived mesenchymal stem cells prevent liver fibrosis via autophagy activation. J Cell Mol Med. 2017;21:2491–502.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  69. 69.

    Yang J, Zhang X, Chen X, Wang L, Yang G. Exosome mediated delivery of miR-124 promotes neurogenesis after ischemia. Mol Ther Nucleic Acids. 2017;7:278–87.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  70. 70.

    Dominguez JM, Dominguez JH, Xie D, Kelly K. Human extracellular microvesicles from renal tubules reverse kidney ischemia-reperfusion injury in rats. PLoS One. 2018;13:e0202550.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  71. 71.

    Webb RL, Kaiser EE, Jurgielewicz BJ, Spellicy S, Scoville SL, Thompson TA, et al. Human neural stem cell extracellular vesicles improve recovery in a porcine model of ischemic stroke. Stroke. 2018;49:1248–56.

    PubMed  PubMed Central  Article  Google Scholar 

  72. 72.

    Webb RL, Kaiser EE, Scoville SL, Thompson TA, Fatima S, Pandya C, et al. Human neural stem cell extracellular vesicles improve tissue and functional recovery in the murine thromboembolic stroke model. Transl Stroke Res. 2018;9:530–9.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  73. 73.

    Caplan AI, Dennis JE. Mesenchymal stem cells as trophic mediators. J Cell Biochem. 2006;98:1076–84.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  74. 74.

    Ferreira JR, Teixeira GQ, Santos SG, Barbosa MA, Almeida-Porada G, Goncalves RM. Mesenchymal stromal cell secretome: influencing therapeutic potential by cellular pre-conditioning. Front Immunol. 2018;9:2837.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  75. 75.

    Simonson OE, Mougiakakos D, Heldring N, Bassi G, Johansson HJ, Dalen M, et al. In vivo effects of mesenchymal stromal cells in two patients with severe acute respiratory distress syndrome. Stem Cells Transl Med. 2015;4:1199–213.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  76. 76.

    Liu C, Su C. Design strategies and application progress of therapeutic exosomes. Theranostics. 2019;9:1015–28.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  77. 77.

    Preciado S, Muntion S, Sanchez-Guijo F. Improving hematopoietic engraftment: Potential role of mesenchymal stromal cell-derived extracellular vesicles. Stem Cells. 2021;39:26–32.

    PubMed  PubMed Central  Google Scholar 

  78. 78.

    Park DJ, Yun WS, Kim WC, Park JE, Lee SH, Ha S, et al. Improvement of stem cell-derived exosome release efficiency by surface-modified nanoparticles. J Nanobiotechnology. 2020;18:178.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  79. 79.

    Ambattu LA, Ramesan S, Dekiwadia C, Hanssen E, Li H, Yeo LY. High frequency acoustic cell stimulation promotes exosome generation regulated by a calcium-dependent mechanism. Commun Biol. 2020;3:553.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  80. 80.

    Messenger SW, Woo SS, Sun Z, Martin TFJ. A Ca2+-stimulated exosome release pathway in cancer cells is regulated by Munc13-4. J Cell Biol. 2018;217:2877–90.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  81. 81.

    Savina A, Furlán M, Vidal M, Colombo MI. Exosome release is regulated by a calcium-dependent mechanism in K562 cells. J Biol Chem. 2003;278:20083–90.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  82. 82.

    Shyong YJ, Chang KC, Lin FH. Calcium phosphate particles stimulate exosome secretion from phagocytes for the enhancement of drug delivery. Colloids Surf B Biointerfaces. 2018;171:391–7.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  83. 83.

    Iliev D, Strandskog G, Nepal A, Aspar A, Olsen R, Jørgensen J, et al. Stimulation of exosome release by extracellular DNA is conserved across multiple cell types. FEBS J. 2018;285:3114–33.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  84. 84.

    Emam SE, Ando H, Abu Lila AS, Shimizu T, Ukawa M, Okuhira K, et al. A novel strategy to increase the yield of exosomes (extracellular vesicles) for an expansion of basic research. Biol Pharm Bull. 2018;41:733–42.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  85. 85.

    Novo D, Heath N, Mitchell L, Caligiuri G, MacFarlane A, Reijmer D, et al. Mutant p53s generate pro-invasive niches by influencing exosome podocalyxin levels. Nat Commun. 2018;9:5069.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  86. 86.

    Parolini I, Federici C, Raggi C, Lugini L, Palleschi S, De Milito A, et al. Microenvironmental pH is a key factor for exosome traffic in tumor cells. J Biol Chem. 2009;284:34211–22.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  87. 87.

    Wang Z, Maruyama K, Sakisaka Y, Suzuki S, Tada H, Suto M, et al. Cyclic stretch force induces periodontal ligament cells to secrete exosomes that suppress IL-1 beta production through the inhibition of the NF-kappa B signaling pathway in macrophages. Front Immunol. 2019;10:1310.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  88. 88.

    King HW, Michael MZ, Gleadle JM. Hypoxic enhancement of exosome release by breast cancer cells. BMC Cancer. 2012;12:421.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  89. 89.

    Sinha S, Hoshino D, Hong NH, Kirkbride KC, Grega-Larson NE, Seiki M, et al. Cortactin promotes exosome secretion by controlling branched actin dynamics. J Cell Biol. 2016;214:197–213.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  90. 90.

    Böker KO, Lemus-Diaz N, Rinaldi Ferreira R, Schiller L, Schneider S, Gruber J. The impact of the CD9 tetraspanin on lentivirus infectivity and exosome secretion. Mol Ther. 2018;26:634–47.

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  91. 91.

    Jabbari N, Nawaz M, Rezaie J. Ionizing radiation increases the activity of exosomal secretory pathway in MCF-7 human breast cancer cells: a possible way to communicate resistance against radiotherapy. Int J Mol Sci. 2019;20:3649.

    CAS  PubMed Central  Article  Google Scholar 

  92. 92.

    Yang Z, Shi J, Xie J, Wang Y, Sun J, Liu T, et al. Large-scale generation of functional mRNA-encapsulating exosomes via cellular nanoporation. Nat Biomed Eng. 2020;4:69–83.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  93. 93.

    Patel DB, Santoro M, Born LJ, Fisher JP, Jay SM. Towards rationally designed biomanufacturing of therapeutic extracellular vesicles: impact of the bioproduction microenvironment. Biotechnol Adv. 2018;36:2051–9.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  94. 94.

    Watson DC, Bayik D, Srivatsan A, Bergamaschi C, Valentin A, Niu G, et al. Efficient production and enhanced tumor delivery of engineered extracellular vesicles. Biomaterials. 2016;105:195–205.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  95. 95.

    Eirin A, Riester SM, Zhu XY, Tang H, Evans JM, O’Brien D, et al. MicroRNA and mRNA cargo of extracellular vesicles from porcine adipose tissue-derived mesenchymal stem cells. Gene. 2014;551:55–64.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  96. 96.

    De Rubis G, Rajeev Krishnan S, Bebawy M. Liquid biopsies in cancer diagnosis, monitoring, and prognosis. Trends Pharmacol Sci. 2019;40:172–86.

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  97. 97.

    Xiao YW, Zhong JN, Zhong BY, Huang JY, Jiang LX, Jiang Y, et al. Exosomes as potential sources of biomarkers in colorectal cancer. Cancer Lett. 2020;476:13–22.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  98. 98.

    He C, Zheng S, Luo Y, Wang B. Exosome theranostics: biology and translational medicine. Theranostics. 2018;8:237–55.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  99. 99.

    Mege D, Panicot-Dubois L, Ouaissi M, Robert S, Sielezneff I, Sastre B, et al. The origin and concentration of circulating microparticles differ according to cancer type and evolution: a prospective single-center study. Int J Cancer. 2016;138:939–48.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  100. 100.

    Santoni G, Morelli MB, Amantini C, Battelli N. Urinary markers in bladder cancer: an update. Front Oncol. 2018;8:362.

    PubMed  PubMed Central  Article  Google Scholar 

  101. 101.

    Wang Q, Yu G, He H, Zheng Z, Li X, Lin R, et al. Differential expression of circular RNAs in bone marrow-derived exosomes from essential thrombocythemia patients. Cell Biol Int. 2021;45:869–81.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  102. 102.

    Zhang P, Liang T, Chen Y, Wang X, Wu TL, Xie ZX, et al. Circulating exosomal miRNAs as novel biomarkers for stable coronary artery disease. Biomed Res Int. 2020;2020:3593962.

    PubMed  PubMed Central  Google Scholar 

  103. 103.

    Zhang LY, Yang X, Wang SB, Chen H, Pan HY, Hu ZM. Membrane derived vesicles as biomimetic carriers for targeted drug delivery system. Curr Top Med Chem. 2020;20:2472–92.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  104. 104.

    Saleh AF, Lazaro-Ibanez E, Forsgard MA, Shatnyeva O, Osteikoetxea X, Karlsson F, et al. Extracellular vesicles induce minimal hepatotoxicity and immunogenicity. Nanoscale. 2019;11:6990–7001.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  105. 105.

    Zhu X, Badawi M, Pomeroy S, Sutaria DS, Xie Z, Baek A, et al. Comprehensive toxicity and immunogenicity studies reveal minimal effects in mice following sustained dosing of extracellular vesicles derived from HEK293T cells. J Extracell Vesicles. 2017;6:1324730.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  106. 106.

    Popowski K, Lutz H, Hu S, George A, Dinh PU, Cheng K. Exosome therapeutics for lung regenerative medicine. J Extracell Vesicles. 2020;9:1785161.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  107. 107.

    Lee JR, Park BW, Kim J, Choo YW, Kim HY, Yoon JK, et al. Nanovesicles derived from iron oxide nanoparticles-incorporated mesenchymal stem cells for cardiac repair. Sci Adv. 2020;6:eaaz0952.

  108. 108.

    Shi X, Cheng Q, Hou T, Han M, Smbatyan G, Lang JE, et al. Genetically engineered cell-derived nanoparticles for targeted breast cancer immunotherapy. Mol Ther. 2020;28:536–47.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  109. 109.

    Ting PJ, Lin CH, Huang FL, Lin MC, Hwang KP, Huang YC, et al. Epidemiology of acute otitis media among young children: a multiple database study in Taiwan. J Microbiol Immunol Infect. 2012;45:453–8.

    PubMed  Article  PubMed Central  Google Scholar 

  110. 110.

    Si Y, Kim S, Zhang E, Tang Y, Jaskula-Sztul R, Markert JM, et al. Targeted exosomes for drug delivery: biomanufacturing, surface tagging, and validation. Biotechnol J. 2020;15:e1900163.

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  111. 111.

    Costafreda MI, Abbasi A, Lu H, Kaplan G. Exosome mimicry by a HAVCR1-NPC1 pathway of endosomal fusion mediates hepatitis A virus infection. Nat Microbiol. 2020;5:1096–106.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  112. 112.

    Ye Y, Zhang X, Xie F, Xu B, Xie P, Yang T, et al. An engineered exosome for delivering sgRNA:Cas9 ribonucleoprotein complex and genome editing in recipient cells. Biomater Sci. 2020;8:2966–76.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  113. 113.

    Kim D, Le QV, Wu Y, Park J, Oh YK. Nanovesicle-mediated delivery systems for CRISPR/Cas genome editing. Pharmaceutics. 2020;12:1233.

    CAS  PubMed Central  Article  Google Scholar 

  114. 114.

    Shao J, Zaro J, Shen Y. Advances in exosome-based drug delivery and tumor targeting: from tissue distribution to intracellular fate. Int J Nanomedicine. 2020;15:9355–71.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  115. 115.

    Wang J, Li W, Zhang L, Ban L, Chen P, Du W, et al. Chemically edited exosomes with dual ligand purified by microfluidic device for active targeted drug delivery to tumor cells. ACS Appl Mater Interfaces. 2017;9:27441–52.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  116. 116.

    Burgio S, Noori L, Marino Gammazza A, Campanella C, Logozzi M, Fais S, et al. Extracellular vesicles-based drug delivery systems: a new challenge and the exemplum of malignant pleural mesothelioma. Int J Mol Sci. 2020;21:5432.

    CAS  PubMed Central  Article  Google Scholar 

  117. 117.

    Gudbergsson JM. Extracellular vesicles for targeted drug delivery: triumphs and challenges. Future Med Chem. 2020;12:1285–7.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  118. 118.

    Luan X, Sansanaphongpricha K, Myers I, Chen H, Yuan H, Sun D. Engineering exosomes as refined biological nanoplatforms for drug delivery. Acta Pharmacol Sin. 2017;38:754–63.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  119. 119.

    Patil SM, Sawant SS, Kunda NK. Exosomes as drug delivery systems: a brief overview and progress update. Eur J Pharm Biopharm. 2020;154:259–69.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

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Acknowledgements

This research was supported by a Grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health and Welfare, Republic of Korea (Grant No.: HI19C1334). and by the National Research Foundation of Korea(NRF) grant funded by the Korea government(MSIT) (No. NRF-2020R1A2C1009789).

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Park, D.J., Seo, Y.J. Engineering of Extracellular Vesicles Based on Payload Changes for Tissue Regeneration. Tissue Eng Regen Med (2021). https://doi.org/10.1007/s13770-021-00349-w

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Keywords

  • Mesenchymal stem cell
  • Extracellular vesicle
  • Regeneration
  • Engineering
  • Medicine