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New therapeutic approach with extracellular vesicles from stem cells for interstitial cystitis/bladder pain syndrome

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Interstitial cystitis/bladder pain syndrome (IC/BPS) is a debilitating chronic disorder characterized by suprapubic pain and urinary symptoms such as urgency, nocturia, and frequency. The prevalence of IC/BPS is increasing as diagnostic criteria become more comprehensive. Conventional pharmacotherapy against IC/BPS has shown suboptimal effects, and consequently, patients with end-stage IC/BPS are subjected to surgery. The novel treatment strategies should have two main functions, anti-inflammatory action and the regeneration of glycosaminoglycan and urothelium layers. Stem cell therapy has been shown to have dual functions. Mesenchymal stem cells (MSCs) are a promising therapeutic option for IC/BPS, but they come with several shortcomings, such as immune activation and tumorigenicity. MSC-derived extracellular vesicles (MSC-EVs) hold numerous therapeutic cargos and are thus a viable cell-free therapeutic option. In this review, we provide a brief overview of IC/BPS pathophysiology and limitations of the MSC-based therapies. Then we provide a detailed explanation and discussion of therapeutic applications of EVs in IC/BPS as well as the possible mechanisms. We believe our review will give an insight into the strengths and drawbacks of EV-mediated IC/BPS therapy and will provide a basis for further development.

Abstract

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a debilitating chronic disorder characterized by suprapubic pain and urinary symptoms such as urgency, nocturia, and frequency. The prevalence of IC/BPS is increasing as diagnostic criteria become more comprehensive. Conventional pharmacotherapy against IC/BPS has shown suboptimal effects, and consequently, patients with end-stage IC/BPS are subjected to surgery. The novel treatment strategies should have two main functions, anti-inflammatory action and the regeneration of glycosaminoglycan and urothelium layers. Stem cell therapy has been shown to have dual functions. Mesenchymal stem cells (MSCs) are a promising therapeutic option for IC/BPS, but they come with several shortcomings, such as immune activation and tumorigenicity. MSC-derived extracellular vesicles (MSC-EVs) hold numerous therapeutic cargos and are thus a viable cell-free therapeutic option. In this review, we provide a brief overview of IC/BPS pathophysiology and limitations of the MSC-based therapies. Then we provide a detailed explanation and discussion of therapeutic applications of EVs in IC/BPS as well as the possible mechanisms. We believe our review will give an insight into the strengths and drawbacks of EV-mediated IC/BPS therapy and will provide a basis for further development.

참고문헌 (99)

  1. McDermott P, "Painful bladder syndrome", interstitial cystitis(history, epidemiology, symptoms, diagnosis and treatments), 2009, pp.3, 16~23
  2. Suskind AM, "The prevalence and overlap of interstitial cystitis", bladder pain syndrome and chronic prostatitis, J Urol, pp.2013, 189[DOI]
  3. Clemens JQ, "Comparison of baseline urological symptoms in men and women in the MAPP research cohort", J Urol, 193, pp.1554~1558 (2015)
  4. Kim A, "Histopathological characteristics of interstitial cystitis", bladder pain syndrome without Hunner lesion, 2017, pp.71, 415~424
  5. Bo K, "An International Urogynecological Association(IUGA)", International Continence Society(ICS)joint report on the terminology for the conservative and nonpharmacological management of female pelvic floor dysfunction, 2017, pp.28, 191~213
  6. Ogawa T, "Current and emerging drugs for interstitial cystitis", bladder pain syndrome(IC, Expert Opin Emerg Drugs, pp.2015, 20[DOI]
  7. Hu P, "Role of membrane proteins in permeability barrier function : uroplakin ablation elevates urothelial permeability", Am J Physiol Renal Physiol, 283, pp.F1200~ (2002)
  8. Višnjar T, "Hyperplasia as a mechanism for rapid resealing urothelial injuries and maintaining high transepithelial resistance", Histochem Cell Biol, 137, pp.177~186 (2012)
  9. Sun TT, "Formation of asymmetric unit membrane during urothelial differentiation", Mol Biol Rep, 23, pp.3~11 (1996)
  10. Wu XR, "Uroplakins in urothelial biology, function, and disease", Kidney Int, 75, pp.1153~1165 (2009)
  11. Osborn SL, "Induction of human embryonic and induced pluripotent stem cells into urothelium", Stem Cells Transl Med, 3, pp.610~619 (2014)
  12. Colopy SA, "A population of progenitor cells in the basal and intermediate layers of the murine bladder urothelium contributes to urothelial development and regeneration", Dev Dyn, 243, pp.988~998 (2014)
  13. Wang C, "Urothelial generation and regeneration in development, injury, and cancer", Dev Dyn, 246, pp.336~343 (2017)
  14. Petrovic V, "Tissue engineering of the urinary bladder : current concepts and future perspectives", TheScientificWorldJOURNAL, 11, pp.1479~1488 (2011)
  15. Hautmann RE, "Urinary diversion : ileal conduit to neobladder", Urol, 169, pp.834~842 (2003)
  16. Abdal Dayem A, "Application of adult and pluripotent stem cells in interstitial cystitis", bladder pain syndrome therapy : methods and perspectives, 2020, pp.9, 766~
  17. Hanno PM, "Diagnosis and treatment of interstitial cystitis", bladder pain syndrome : AUA guideline amendment, 2015, pp.193, 1545~1553
  18. Shin JH, "Current and future directions of stem cell therapy for bladder dysfunction", Stem Cell Rev Rep, 16, pp.82~93 (2020)
  19. Tabata H, "Possible role of intravenous administration of mesenchymal stem cells to alleviate interstitial cystitis", bladder pain syndrome in a Toll-like receptor-7 agonist-induced experimental animal model in rat, 2021, pp.21, 156~
  20. Bateman ME, "Concise review : using fat to fight disease : a systematic review of nonhomologous adipose-derived stromal", stem cell therapies, 2018, pp.36, 1311~1328
  21. Borakati A, "A systematic review and meta-analysis of clinical trials of mesenchymal stem cell therapy for cartilage repair", Curr Stem Cell Res Ther, 13, pp.215~225 (2018)
  22. Yim H, "Safety of mesenchymal stem cell therapy : a systematic review and meta-analysis", Cytotherapy, 18, pp.S132~ (2016)
  23. Lener T, "Applying extracellular vesicles based therapeutics in clinical trials–an ISEV position paper", J Extracell Vesicles, 4, pp.30087~ (2015)
  24. Witwer KW, "Defining mesenchymal stromal cell(MSC)-derived small extracellular vesicles for therapeutic applications", J Extracell Vesicles, 8, pp.1609206~ (2019)
  25. Alvarez-Erviti L, "Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes", Nat Biotechnol, 29, pp.341~345 (2011)
  26. Cloutier N, "Platelets can enhance vascular permeability", Blood, 120, pp.1334~1343 (2012)
  27. Wahlgren J, "Plasma exosomes can deliver exogenous short interfering RNA to monocytes and lymphocytes", Nucleic Acids Res, 40, pp.e130~ (2012)
  28. Ohno S-i, "Systemically injected exosomes targeted to EGFR deliver antitumor microRNA to breast cancer cells", Mol Ther, 21, pp.185~191 (2013)
  29. Akao Y, "Microvesicle-mediated RNA molecule delivery system using monocytes", macrophages, 2011, pp.19, 395~399
  30. Théry C, "Membrane vesicles as conveyors of immune responses", Nat Rev Immunol, 9, pp.581~593 (2009)
  31. Buzas EI, "Emerging role of extracellular vesicles in inflammatory diseases", Nat Rev Rheumatol, 10, pp.356~364 (2014)
  32. Börger V, "Mesenchymal stem", stromal cell-derived extracellular vesicles and their potential as novel immunomodulatory therapeutic agents, 2017, pp.18, 1450~
  33. McLennan MT, "Interstitial cystitis : epidemiology, pathophysiology, and clinical presentation", Obstet Gynecol Clin, 41, pp.385~395 (2014)
  34. 김현정, "Update on the Pathology and Diagnosis of Interstitial Cystitis", Bladder Pain Syndrome: A Review, 2016, pp.20(1), 13~17[DOI]
  35. Yoshimura N, "Bladder afferent hyperexcitability in bladder pain syndrome", interstitial cystitis, 2014, pp.21, 18~25
  36. Lewis SA, "Everything you wanted to know about the bladder epithelium but were afraid to ask", Am J Physiol Renal Physiol, 278, pp.F867~ (2000)
  37. Neuhaus J, "Structure and function of suburothelial myofibroblasts in the human urinary bladder under normal and pathological conditions", Der Urologe Ausg A, 46, pp.1197~1202 (2007)
  38. Parsons CL, "The role of a leaky epithelium and potassium in the generation of bladder symptoms in interstitial cystitis", overactive bladder, urethral syndrome, prostatitis and gynaecological chronic pelvic pain, 2011, pp.107, 370~375
  39. Birder L, "Urothelial signaling", Physiol Rev, 93, pp.653~680 (2013)
  40. Lopez SR, "Current standard of care in treatment of bladder pain syndrome", interstitial cystitis, 2021, pp.13, 17562872211022478~
  41. Warren JW, "Urinary tract infection and inflammation at onset of interstitial cystitis", painful bladder syndrome, 2008, pp.71, 1085~1090
  42. Shea-Donohue T, "Mast cells", Curr Gastroenterol Rep, 12, pp.349~357 (2010)
  43. Gamper M, "Are mast cells still good biomarkers for bladder pain syndrome", interstitial cystitis?, 2015, pp.193, 1994~2000
  44. Van De Merwe JP, "Interstitial cystitis and systemic autoimmune diseases", Nat Clin Pract Urol, 4, pp.484~491 (2007)
  45. Lee C-K, "Overactive bladder and bladder pain syndrome", interstitial cystitis in primary Sjögren’s syndrome patients : a nationwide population-based study, 2019, pp.14, e0225455~
  46. Phinney DG, "Concise review : msc-derived exosomes for cell-free therapy", Stem Cells, 35, pp.851~858 (2017)
  47. Wu S, "Urothelial differentiation of human umbilical cord-derived mesenchymal stromal cells in vitro", Anal Cell Pathol, 36, pp.63~69 (2013)
  48. Song B, "Bladder smooth muscle cells differentiation from dental pulp stem cells : future potential for bladder tissue engineering", Stem Cells Int, 2016, pp.6979368~ (2016)
  49. Jiang W, "Wnt-GSK3β", β-catenin regulates the differentiation of dental pulp stem cells into bladder smooth muscle cells, 2019, pp.2019, ~
  50. Kim A, "Stem cell therapy for interstitial cystitis", bladder pain syndrome, 2016, pp.17, 1~9
  51. Kuriyan AE, "Vision loss after intravitreal injection of autologous"stem cells"for AMD", N Engl J Med, 376, pp.1047~1053 (2017)
  52. Barkholt L, "Risk of tumorigenicity in mesenchymal stromal cell–based therapies—bridging scientific observations and regulatory viewpoints", Cytotherapy, 15, pp.753~759 (2013)
  53. Herberts CA, "Risk factors in the development of stem cell therapy", J Transl Med, 9, pp.1~14 (2011)
  54. Musiał-Wysocka A, "The pros and cons of mesenchymal stem cell-based therapies", Cell Transplant, 28, pp.801~812 (2019)
  55. Kraitchman DL, "Dynamic imaging of allogeneic mesenchymal stem cells trafficking to myocardial infarction", Circulation, 112, pp.1451~1461 (2005)
  56. McBride C, "Quantifying levels of transplanted murine and human mesenchymal stem cells in vivo by realtime PCR", Cytotherapy, 5, pp.7~18 (2003)
  57. François S, "Local irradiation not only induces homing of human mesenchymal stem cells at exposed sites but promotes their widespread engraftment to multiple organs : a study of their quantitative distribution after irradiation damage", Stem cells, 24, pp.1020~1029 (2006)
  58. Toma C, "Fate of culture-expanded mesenchymal stem cells in the microvasculature : in vivo observations of cell kinetics", Circ Res, 104, pp.398~402 (2009)
  59. Wei W, "Mesenchymal stem cell–derived exosomes : a promising biological tool in nanomedicine", Front Pharmacol, 11, pp.590470~ (2021)
  60. Kuret T, "A systematic review of therapeutic approaches used in experimental models of interstitial cystitis", bladder pain syndrome, 2021, pp.9, 865~
  61. da Silva Meirelles L, "In search of the in vivo identity of mesenchymal stem cells", Stem cells, 26, pp.2287~2299 (2008)
  62. Caplan AI, "The MSC : an injury drugstore", Cell Stem Cell, 9, pp.11~15 (2011)
  63. Gnecchi M, "Paracrine action accounts for marked protection of ischemic heart by Akt-modified mesenchymal stem cells", Nat Med, 11, pp.367~368 (2005)
  64. Goolaerts A, "Conditioned media from mesenchymal stromal cells restore sodium transport and preserve epithelial permeability in an in vitro model of acute alveolar injury", Am J Physiol-Lung Cell Mol Physiol, 306, pp.L975~ (2014)
  65. Tremain N, "MicroSAGE analysis of 2, 353expressed genes in a single cell-derived colony of undifferentiated human mesenchymal stem cells reveals mRNAs of multiple cell lineages", Stem Cells, 19, pp.408~418 (2001)
  66. Ren J, "Global transcriptome analysis of human bone marrow stromal cells(BMSC)reveals proliferative, mobile and interactive cells that produce abundant extracellular matrix proteins, some of which may affect BMSC potency", Cytotherapy, 13, pp.661~674 (2011)
  67. Tian H, "Myogenic differentiation of human bone marrow mesenchymal stem cells on a 3D nano fibrous scaffold for bladder tissue engineering", Biomaterials, 31, pp.870~877 (2010)
  68. Sharma AK, "Urinary bladder smooth muscle regeneration utilizing bone marrow derived mesenchymal stem cell seeded elastomeric poly(1, 8-octanediol-co-citrate)based thin films", Biomaterials, 31, pp.6207~6217 (2010)
  69. Zhang Y, "Growth of bone marrow stromal cells on small intestinal submucosa : an alternative cell source for tissue engineered bladder", BJU Int, 96, pp.1120~1125 (2005)
  70. Ohishi M, "Bone marrow mesenchymal stem cells", J Cell Biochem, 109, pp.277~282 (2010)
  71. Yu B, "Exosomes secreted from GATA-4 overexpressing mesenchymal stem cells serve as a reservoir of anti-apoptotic microRNAs for cardioprotection", Int J Cardiol, 182, pp.349~360 (2015)
  72. Mendt M, "Mesenchymal stem cell-derived exosomes for clinical use", Bone Marrow Transplant, 54, pp.789~792 (2019)
  73. Wen C, "Roles of mesenchymal stem cells and exosomes in interstitial cystitis", bladder pain syndrome, 2022, pp.26, 624~635
  74. Parekkadan B, "Mesenchymal stem cells as therapeutics", Annu Rev Biomed Eng, 12, pp.87~117 (2010)
  75. Kang H, "Methods to isolate extracellular vesicles for diagnosis", Micro Nano Syst Lett, 5, pp.15~ (2017)
  76. Zhao Z, "Isolation and analysis methods of extracellular vesicles(EVs)", Extracell Vesicles Circ Nucl Acids, 2, pp.80~103 (2021)
  77. Théry C, "Minimal information for studies of extracellular vesicles 2018(MISEV 2018) : a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines", J Extracell Vesicles, 7, pp.1535750~ (2018)
  78. Ludwig N, "Challenges in exosome isolation and analysis in health and disease", Int J Mol Sci, 20, pp.4684~ (2019)
  79. Harding C, "Receptor-mediated endocytosis of transferrin and recycling of the transferrin receptor in rat reticulocytes", J Cell Biol, 97, pp.329~339 (1983)
  80. Cocucci E, "Ectosomes and exosomes : shedding the confusion between extracellular vesicles", Trends Cell Biol, 25, pp.364~372 (2015)
  81. Lai RC, "Mesenchymal stem cell exosomes", Semin Cell Dev Biol, 40, pp.82~88 (2015)
  82. Giebel B, "Clinical potential of mesenchymal stem", stromal cell-derived extracellular vesicles, 2017, pp.4, 84~
  83. Yeo RWY, "Exosomes and their therapeutic applications", ADVANCES IN PHARMACEUTICAL CELL THERAPY: Principles of Cell-Based Biopharmaceuticals, pp.477~501 (2016)
  84. Toh WS, "MSC exosome as a cell-free MSC therapy for cartilage regeneration : implications for osteoarthritis treatment", Semin Cell Dev Biol, 67, pp.56~64 (2017)
  85. Zhang S, "MSC exosomes mediate cartilage repair by enhancing proliferation, attenuating apoptosis and modulating immune reactivity", Biomaterials, 156, pp.16~27 (2018)
  86. Hu S, "Platelet membrane and stem cell exosome hybrids enhance cellular uptake and targeting to heart injury", Nano Today, 39, pp.101210~ (2021)
  87. Popowski KD, "Exosome therapeutics for COVID-19 and respiratory viruses", View(Beijing), 2, pp.20200186~ (2021)
  88. Gonzalez-King H, "Hypoxia inducible factor-1α potentiates jagged 1-mediated angiogenesis by mesenchymal stem cell-derived exosomes", Stem Cells, 35, pp.1747~1759 (2017)
  89. Anderson JD, "Comprehensive proteomic analysis of mesenchymal stem cell exosomes reveals modulation of angiogenesis via nuclear factor-kappaB signaling", Stem Cells, 34, pp.601~613 (2016)
  90. Adamowicz J, "Conditioned medium derived from mesenchymal stem cells culture as a intravesical therapy for cystitis interstitials", Med Hypotheses, 82, pp.670~673 (2014)
  91. Xie J, "Umbilical cord-derived mesenchymal stem cells alleviated inflammation and inhibited apoptosis in interstitial cystitis via AKT", mTOR signaling pathway, 2018, pp.495, 546~552
  92. Wiafe B, "Hypoxia-increased expression of genes involved in inflammation, dedifferentiation, pro-fibrosis, and extracellular matrix remodeling of human bladder smooth muscle cells", In Vitro Cell Dev Biol Anim, 53, pp.58~66 (2017)
  93. Wiafe B, "Mesenchymal stem cells inhibit hypoxia-induced inflammatory and fibrotic pathways in bladder smooth muscle cells", World J Urol, 36, pp.1157~1165 (2018)
  94. Jian-Wei Lv, "Inhibition of microRNA-214 promotes epithelial mesenchymal transition process and induces interstitial cystitis in postmenopausal women by upregulating Mfn2", Experimental and Molecular Medicine, 49, pp.1~11 (2017), 생화학분자생물학회
  95. Wang Y, "Exosomes derived from miR-214-enriched bone marrow-derived mesenchymal stem cells regulate oxidative damage in cardiac stem cells by targeting CaMKII", Oxid Med Cell Longev, 2018, pp.4971261~ (2018)
  96. Yang C, "Anti-inflammatory effects of mesenchymal stem cell-derived exosomal microRNA-146a-5p and microRNA-548e-5p on human trophoblast cells", Mol Hum Reprod, 25, pp.755~771 (2019)
  97. Li Y, "Exosomes derived from human adipose mesenchymal stem cells attenuate hypertrophic scar fibrosis by miR-192-5p", IL-17RA, Stem Cell Res Ther, pp.2021, 12[DOI]
  98. Xie L, "Therapeutic potential of exosomes in pulmonary fibrosis", Front pharmacol, 11, pp.590972~590972 (2020)
  99. Tavasolian F, "miRNA-146a improves immunomodulatory effects of MSCderived exosomes in rheumatoid arthritis", Curr Gene Ther, 20, pp.297~312 (2020)

관련 논문AI추천

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