Application of extracellular vesicles in the treatment of inflammatory bowel disease

authors:

avatar neda heidari , avatar Hajar Abbasi , avatar Kaveh Baghaei , avatar Saeed Namaki , * , avatar Seyed Mahmoud Hashemi

Koomesh: Vol.22, issue 2; 209-219
published online: August 02, 2020
article type: issue_documents_importer
received: January 03, 2019
accepted: August 02, 2019

how to cite: heidari N, Abbasi H, Baghaei K, Namaki S, Hashemi S M. Application of extracellular vesicles in the treatment of inflammatory bowel disease. koomesh. 2020;22(2):e153171. 

Abstract

Introduction: Inflammatory bowel disease(IBD) is caused by genetic, environmental, microbial and immune factors. IBD has two primary forms: Ulcerative colitis and Crohn´s disease. The incidence of IBD has significantly increased over the last few decades. Given that patients have poor response to drug treatments or are resistant to drug therapies, new therapies are needed for gastrointestinal inflammatory disease treatments. Most types of cells including mesenchymal stem cells produce extracellular vesicles, which play a vital role in cell-to-cell communication. Extracellular vesicles, depending on their contents, can stimulate or suppress immune responses. In recent years, stem cells derived extracellular vesicles have been used as agents for autoimmune and inflammatory disease treatments. In these studies, stem cells-derived extracellular vesicles have been shown to improve inflammatory conditions. in this review, we summarize the therapeutic uses of extracellular vesicles in regulating immune responses in inflammatory bowel disease

References

  • 1.

    Kaser A, Zeissig S, Blumberg RS. Inflammatory bowel disease. Annu Rev Immunol 2010; 28: 573-621.

  • 2.

    Loftus EV, Jr. Clinical epidemiology of inflammatory bowel disease: Incidence, prevalence, and environmental influences. Gastroenterology 2004; 126: 1504-1517.

  • 3.

    Abraham C, Cho JH. Inflammatory bowel disease. N Engl J Med 2009; 361: 2066-2078.

  • 4.

    Ananthakrishnan AN. Epidemiology and risk factors for IBD. Nat Rev Gastroenterol Hepatol 2015; 12: 205-217.

  • 5.

    Andres PG, Friedman LS. Epidemiology and the natural course of inflammatory bowel disease. Gastroenterol Clin North Am 1999; 28: 255-281.

  • 6.

    Hanauer SB. Inflammatory bowel disease: epidemiology, pathogenesis, and therapeutic opportunities. Inflamm Bowel Dis 2006; 12: S3-9.

  • 7.

    Zhang YZ, Li YY. Inflammatory bowel disease: pathogenesis. World J Gastroenterol 2014; 20: 91-99.

  • 8.

    Abdel Salam AG, Ata HM, Salman TM, Rashed LA, Sabry D, Schaalan MF. Potential therapeutic utility of mesenchymal stem cells in inflammatory bowel disease in mice. Int Immunopharmacol 2014; 22: 515-521.

  • 9.

    Eastaff-Leung N, Mabarrack N, Barbour A, Cummins A, Barry S. Foxp3+ regulatory T cells, Th17 effector cells, and cytokine environment in inflammatory bowel disease. J Clin Immunol 2010; 30: 80-89.

  • 10.

    Dave M, Mehta K, Luther J, Baruah A, Dietz AB, Faubion WA, Jr. Mesenchymal stem cell therapy for inflammatory bowel disease: a systematic review and meta-analysis. Inflamm Bowel Dis 2015; 21: 2696-2707.

  • 11.

    Pithadia AB, Jain S. Treatment of inflammatory bowel disease (IBD). Pharmacol Rep 2011; 63: 629-642.

  • 12.

    Newman RE, Yoo D, LeRoux MA, Danilkovitch-Miagkova A. Treatment of inflammatory diseases with mesenchymal stem cells. Inflamm Allergy Drug Targets 2009; 8: 110-123.

  • 13.

    Yamanishi H, Murakami H, Ikeda Y, Abe M, Kumagi T, Hiasa Y, et al. Regulatory dendritic cells pulsed with carbonic anhydrase I protect mice from colitis induced by CD4+CD25- T cells. J Immunol 2012; 188: 2164-2172.

  • 14.

    Sales-Campos H, Basso PJ, Alves VB, Fonseca MT, Bonfa G, Nardini V, Cardoso CR. Classical and recent advances in the treatment of inflammatory bowel diseases. Braz J Med Biol Res 2015; 48: 96-107.

  • 15.

    Wei X, Yang X, Han ZP, Qu FF, Shao L, Shi YF. Mesenchymal stem cells: a new trend for cell therapy. Acta Pharmacol Sin 2013; 34: 747-754.

  • 16.

    Ren G, Zhang L, Zhao X, Xu G, Zhang Y, Roberts AI, et al. Mesenchymal stem cell-mediated immunosuppression occurs via concerted action of chemokines and nitric oxide. Cell Stem Cell 2008; 2: 141-150.

  • 17.

    Cocucci E, Racchetti G, Meldolesi J. Shedding microvesicles: artefacts no more. Trends Cell Biol 2009; 19: 43-51.

  • 18.

    Yoon YJ, Kim OY, Gho YS. Extracellular vesicles as emerging intercellular communicasomes. BMB Rep 2014; 47: 531-539.

  • 19.

    Chaput N, Thery C. Exosomes: immune properties and potential clinical implementations. Semin Immunopathol 2011; 33: 419-440.

  • 20.

    Mahmoudi M, Taghavi-Farahabadi M, Rezaei N, Hashemi SM. Comparison of the effects of adipose tissue mesenchymal stromal cell-derived exosomes with conditioned media on neutrophil function and apoptosis. Int Immunopharmacol 2019; 74: 105689.

  • 21.

    Guo W, Gao Y, Li N, Shao F, Wang C, Wang P, et al. Exosomes: New players in cancer (Review). Oncol Rep 2017; 38: 665-675.

  • 22.

    Mahmoudi M, Taghavi M, Hashemi SM. Exosomes: mediators of immune regulation. Immunoregulation 2018; 121-126.

  • 23.

    Selmaj I, Mycko MP, Raine CS, Selmaj KW. The role of exosomes in CNS inflammation and their involvement in multiple sclerosis. J Neuroimmunol 2017; 306: 1-10.

  • 24.

    Nojehdehi S HS. Isolation and characterization of exosomes seperated from stem cells by ultra-centrifuge method. Res Med 2017; 244-250.

  • 25.

    Colombo M, Raposo G, Thery C. Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annu Rev Cell Dev Biol 2014; 30: 255-289.

  • 26.

    Munich S, Sobo-Vujanovic A, Buchser WJ, Beer-Stolz D, Vujanovic NL. Dendritic cell exosomes directly kill tumor cells and activate natural killer cells via TNF superfamily ligands. Oncoimmunology 2012; 1: 1074-1083.

  • 27.

    Thery C, Ostrowski M, Segura E. Membrane vesicles as conveyors of immune responses. Nat Rev Immunol 2009; 9: 581-593.

  • 28.

    Edgar JR. QA: What are exosomes, exactly? BMC Biol 2016; 14: 46.

  • 29.

    Isola AL, Chen S. Exosomes: the messengers of health and disease. Curr Neuropharmacol 2017; 15: 157-165.

  • 30.

    Rana S, Zoller M. Exosome target cell selection and the importance of exosomal tetraspanins: a hypothesis. Biochem Soc Trans 2011; 39: 559-562.

  • 31.

    Tokhanbigli S, Baghaei K, Asadirad A, Hashemi SM, Asadzadeh-Aghdaei H, Zali MR. Immunoregulatory impact of human mesenchymal-conditioned media and mesenchymal derived exosomes on monocytes. Mol Biol Res Commun 2019; 8: 79-89.

  • 32.

    Shojaei S, Hashemi SM, Ghanbarian H, Salehi M, Mohammadi-Yeganeh S. Effect of mesenchymal stem cells-derived exosomes on tumor microenvironment: Tumor progression versus tumor suppression. J Cell Physiol 2019; 234: 3394-3409.

  • 33.

    Corrado C, Raimondo S, Chiesi A, Ciccia F, De Leo G, Alessandro R. Exosomes as intercellular signaling organelles involved in health and disease: basic science and clinical applications. Int J Mol Sci 2013; 14: 5338-5366.

  • 34.

    Barros FM, Carneiro F, Machado JC, Melo SA. Exosomes and Immune Response in Cancer: Friends or Foes? Front Immunol 2018; 9: 730.

  • 35.

    Robbins PD, Morelli AE. Regulation of immune responses by extracellular vesicles. Nat Rev Immunol 2014; 14: 195-208.

  • 36.

    Cloutier N, Pare A, Farndale RW, Schumacher HR, Nigrovic PA, Lacroix S, Boilard E. 2012. Platelets can enhance vascular permeability. Blood 2012; 120: 1334-1343.

  • 37.

    Bianco NR, Kim SH, Ruffner MA, Robbins PD. Therapeutic effect of exosomes from indoleamine 2,3-dioxygenase-positive dendritic cells in collagen-induced arthritis and delayed-type hypersensitivity disease models. Arthritis Rheum 2009; 60: 380-389.

  • 38.

    Kim SH, Lechman ER, Bianco N, Menon R, Keravala A, Nash J, et al. Exosomes derived from IL-10-treated dendritic cells can suppress inflammation and collagen-induced arthritis. J Immunol 2005; 174: 6440-6448.

  • 39.

    Mokarizadeh A, Delirezh N, Morshedi A, Mosayebi G, Farshid AA, Mardani K. Microvesicles derived from mesenchymal stem cells: potent organelles for induction of tolerogenic signaling. Immunol Lett 2012; 147: 47-54.

  • 40.

    Perez-Hernandez J, Redon J, Cortes R. Extracellular vesicles as therapeutic agents in systemic lupus erythematosus. Int J Mol Sci 2017; 18.

  • 41.

    Tan L, Wu H, Liu Y, Zhao M, Li D, Lu Q. Recent advances of exosomes in immune modulation and autoimmune diseases. Autoimmunity 2016; 49: 357-365.

  • 42.

    Sharma J, Hampton JM, Valiente GR, Wada T, Steigelman H, Young MC, et al. Therapeutic development of mesenchymal stem cells or their extracellular vesicles to inhibit autoimmune-mediated inflammatory processes in systemic lupus erythematosus. Front Immunol 2017; 8: 526.

  • 43.

    Pezeshki Naraghi S, Hashemi SM. Immunomodulatory effect of mesenchymal stem cells in multiple sclerosis and experimental autoimmune encephalomyelitis: a review study. Immunoregulation 2018; 1: 67-80.

  • 44.

    Nojehdehi S, Soudi S, Hesampour A, Rasouli S, Soleimani M, Hashemi SM. Immunomodulatory effects of mesenchymal stem cell-derived exosomes on experimental type-1 autoimmune diabetes. J Cell Biochem 2018; 119: 9433-9443.

  • 45.

    Fujii S, Miura Y, Fujishiro A, Shindo T, Shimazu Y, Hirai H, et al. Graft-versus-host disease amelioration by human bone marrow mesenchymal stromal/stem cell-derived extracellular vesicles is associated with peripheral preservation of naive T cell populations. Stem Cells 2018; 36: 434-445.

  • 46.

    Lia G, Brunello L, Bruno S, Carpanetto A, Omede P, Festuccia M, et al. Extracellular vesicles as potential biomarkers of acute graft-vs-host disease. Leukemia 2018; 32: 765-773.

  • 47.

    Xu R, Rai A, Chen M, Suwakulsiri W, Greening DW, Simpson RJ. Extracellular vesicles in cancer - implications for future improvements in cancer care. Nat Rev Clin Oncol 2018; 15: 617-638.

  • 48.

    Lai RC, Chen TS, Lim SK. Mesenchymal stem cell exosome: a novel stem cell-based therapy for cardiovascular disease. Regen Med 2011; 6: 481-492.

  • 49.

    Becker A, Thakur BK, Weiss JM, Kim HS, Peinado H, Lyden D. Extracellular vesicles in cancer: cell-to-cell mediators of metastasis. Cancer Cell 2016; 30: 836-848.

  • 50.

    Mirotsou M, Jayawardena TM, Schmeckpeper J, Gnecchi M, Dzau VJ. Paracrine mechanisms of stem cell reparative and regenerative actions in the heart. J Mol Cell Cardiol 2011; 50: 280-289.

  • 51.

    Li F, Fang R, Rao L, Meng F, Zhao X. [Research progress on exosomes in diagnosis and treatment of cardiovascular diseases]. Zhejiang Da Xue Xue Bao Yi Xue Ban 2018; 47: 320-326.

  • 52.

    Lazar E, Benedek T, Korodi S, Rat N, Lo J, Benedek I. Stem cell-derived exosomes - an emerging tool for myocardial regeneration. World J Stem Cells 2018; 10: 106-115.

  • 53.

    Ma S, Xie N, Li W, Yuan B, Shi Y, Wang Y. Immunobiology of mesenchymal stem cells. Cell Death Differ 2014; 21: 216-225.

  • 54.

    Glennie S, Soeiro I, Dyson PJ, Lam EW, Dazzi F. Bone marrow mesenchymal stem cells induce division arrest anergy of activated T cells. Blood 2005; 105: 2821-2827.

  • 55.

    Krampera M, Cosmi L, Angeli R, Pasini A, Liotta F, Andreini A, et al. Role for interferon-gamma in the immunomodulatory activity of human bone marrow mesenchymal stem cells. Stem Cells 2006; 24: 386-398.

  • 56.

    Baghaei K, Hashemi SM, Tokhanbigli S, Asadi Rad A, Assadzadeh-Aghdaei H, Sharifian A, Zali MR. Isolation, differentiation, and characterization of mesenchymal stem cells from human bone marrow. Gastroenterol Hepatol Bed Bench 2017; 10: 208-213.

  • 57.

    Gonzalez MA, Gonzalez-Rey E, Rico L, Buscher D, Delgado M. Adipose-derived mesenchymal stem cells alleviate experimental colitis by inhibiting inflammatory and autoimmune responses. Gastroenterology 2009; 136: 978-989.

  • 58.

    Kastelein RA, Hunter CA, Cua DJ. Discovery and biology of IL-23 and IL-27: related but functionally distinct regulators of inflammation. Annu Rev Immunol 2007; 25: 221-242.

  • 59.

    Akiyama K, Chen C, Wang D, Xu X, Qu C, Yamaza T, et al. Mesenchymal-stem-cell-induced immunoregulation involves FAS-ligand-/FAS-mediated T cell apoptosis. Cell Stem Cell 2012; 10: 544-555.

  • 60.

    Gonzalez-Rey E, Anderson P, Gonzalez MA, Rico L, Buscher D, Delgado M. Human adult stem cells derived from adipose tissue protect against experimental colitis and sepsis. Gut 2009; 58: 929-939.

  • 61.

    Zuk PA, Zhu M, Ashjian P, De Ugarte DA, Huang JI, Mizuno H, et al. Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell 2002; 13: 4279-4295.

  • 62.

    Kim N, Cho SG. New strategies for overcoming limitations of mesenchymal stem cell-based immune modulation. Int J Stem Cells 2015; 8: 54-68.

  • 63.

    Pouya S, Heidari M, Baghaei K, Asadzadeh Aghdaei H, Moradi A, Namaki S, et al. Study the effects of mesenchymal stem cell conditioned medium injection in mouse model of acute colitis. Int Immunopharmacol 2018; 54: 86-94.

  • 64.

    Le Blanc K, Mougiakakos D. Multipotent mesenchymal stromal cells and the innate immune system. Nat Rev Immunol 2012; 12: 383-396.

  • 65.

    Heidari M, Pouya S, Baghaei K, Aghdaei HA, Namaki S, Zali MR, Hashemi SM. The immunomodulatory effects of adipose-derived mesenchymal stem cells and mesenchymal stem cells-conditioned medium in chronic colitis. J Cell Physiol 2018; 233: 8754-8766.

  • 66.

    Watanabe S, Arimura Y, Nagaishi K, Isshiki H, Onodera K, Nasuno M, et al. Conditioned mesenchymal stem cells produce pleiotropic gut trophic factors. J Gastroenterol 2014; 49: 270-282.

  • 67.

    Ghosh S, Mitchell R. Impact of inflammatory bowel disease on quality of life: results of the european federation of Crohn's and ulcerative colitis associations (EFCCA) patient survey. J Crohns Colitis 2007; 1: 10-20.

  • 68.

    Burrello J, Monticone S, Gai C, Gomez Y, Kholia S, Camussi G. Stem cell-derived extracellular vesicles and immune-modulation. Front Cell Dev Biol 2016; 4: 83.

  • 69.

    Hetzenecker AM, Seidl MC, Kosovac K, Herfarth H, Kellermeier S, Obermeier F, et al. Downregulation of the ubiquitin-proteasome system in normal colonic macrophages and reinduction in inflammatory bowel disease. Digestion 2012; 86: 34-47.

  • 70.

    Cleynen I, Vazeille E, Artieda M, Verspaget HW, Szczypiorska M, Bringer MA, et al. Genetic and microbial factors modulating the ubiquitin proteasome system in inflammatory bowel disease. Gut 2014; 63: 1265-1274.

  • 71.

    Davis KA, Patton JT. Shutdown of interferon signaling by a viral-hijacked E3 ubiquitin ligase. Microb Cell 2017; 4: 387-389.

  • 72.

    Wu Y, Qiu W, Xu X, Kang J, Wang J, Wen Y, et al. Exosomes derived from human umbilical cord mesenchymal stem cells alleviate inflammatory bowel disease in mice through ubiquitination. Am J Transl Res 2018; 10: 2026-2036.

  • 73.

    Sydora BC, MacFarlane SM, Lupicki M, Dmytrash AL, Dieleman LA, Fedorak RN. An imbalance in mucosal cytokine profile causes transient intestinal inflammation following an animal's first exposure to faecal bacteria and antigens. Clin Exp Immunol 2010; 161: 187-196.

  • 74.

    Brito TV, Neto JP, Prudencio RS, Batista JA, Junior JS, Silva RO, et al. Sulfated-polysaccharide fraction extracted from red algae Gracilaria birdiae ameliorates trinitrobenzenesulfonic acid-induced colitis in rats. J Pharm Pharmacol 2014; 66: 1161-1170.

  • 75.

    Zhou YH, Yu JP, Liu YF, Teng XJ, Ming M, Lv P, et al. Effects of Ginkgo biloba extract on inflammatory mediators (SOD, MDA, TNF-alpha, NF-kappaBp65, IL-6) in TNBS-induced colitis in rats. Mediators Inflamm 2006; 2006: 92642.

  • 76.

    Yang J, Liu XX, Fan H, Tang Q, Shou ZX, Zuo DM, et al. Extracellular vesicles derived from bone marrow mesenchymal stem cells protect against Experimental colitis via attenuating colon inflammation, oxidative stress and apoptosis. PLoS One 2015; 10: e0140551.

  • 77.

    Ji T, Xu C, Sun L, Yu M, Peng K, Qiu Y, et al. Aryl hydrocarbon receptor activation down-regulates IL-7 and reduces inflammation in a mouse model of DSS-Induced colitis. Dig Dis Sci 2015; 60: 1958-1966.

  • 78.

    Nemoto Y, Kanai T, Takahara M, Oshima S, Nakamura T, Okamoto R, et al. Bone marrow-mesenchymal stem cells are a major source of interleukin-7 and sustain colitis by forming the niche for colitogenic CD4 memory T cells. Gut 2013; 62: 1142-1152.

  • 79.

    Kleiner G, Zanin V, Monasta L, Crovella S, Caruso L, Milani D, Marcuzzi A. Pediatric patients with inflammatory bowel disease exhibit increased serum levels of proinflammatory cytokines and chemokines, but decreased circulating levels of macrophage inhibitory protein-1beta, interleukin-2 and interleukin-17. Exp Ther Med 2015; 9: 2047-2052.

  • 80.

    Korolkova OY, Myers JN, Pellom ST, Wang L, M'Koma AE. Characterization of serum cytokine profile in predominantly colonic inflammatory bowel disease to delineate ulcerative and crohn's colitides. Clin Med Insights Gastroenterol 2015; 8: 29-44.

  • 81.

    Mao F, Wu Y, Tang X, Kang J, Zhang B, Yan Y, et al. Exosomes derived from human umbilical cord mesenchymal stem cells relieve inflammatory bowel disease in mice. Biomed Res Int 2017; 2017: 5356760.

  • 82.

    Cosin-Roger J, Ortiz-Masia D, Calatayud S, Hernandez C, Esplugues JV, Barrachina MD. The activation of Wnt signaling by a STAT6-dependent macrophage phenotype promotes mucosal repair in murine IBD. Mucosal Immunol 2016; 9: 986-998.

  • 83.

    Cao L, Xu H, Wang G, Liu M, Tian D, Yuan Z. Extracellular vesicles derived from bone marrow mesenchymal stem cells attenuate dextran sodium sulfate-induced ulcerative colitis by promoting M2 macrophage polarization. Int Immunopharmacol 2019; 72: 264-274.

  • 84.

    Eichenberger RM, Ryan S, Jones L, Buitrago G, Polster R, Montes de Oca M, et al. Hookworm secreted extracellular vesicles interact with host cells and prevent inducible colitis in mice. Front Immunol 2018; 9: 850.

  • 85.

    Leoni G, Neumann PA, Kamaly N, Quiros M, Nishio H, Jones HR, et al. Annexin A1-containing extracellular vesicles and polymeric nanoparticles promote epithelial wound repair. J Clin Invest 2015; 125: 1215-1227.

  • 86.

    Ma ZJ, Wang YH, Li ZG, Wang Y, Li BY, Kang HY, Wu XY. Immunosuppressive effect of exosomes from mesenchymal stromal cells in defined medium on experimental colitis. Int J Stem Cells 2019; 12: 440-448.

  • 87.

    Wu H, Fan H, Shou Z, Xu M, Chen Q, Ai C, et al. Extracellular vesicles containing miR-146a attenuate experimental colitis by targeting TRAF6 and IRAK1. Int Immunopharmacol 2019; 68: 204-212.##.