Vestnik dermatologii i venerologiiVestnik dermatologii i venerologiiВестник дерматологии и венерологии0042-46092313-6294Rossijskoe Obschestvo Dermatovenerologov i Kosmetologov1187610.25208/vdv11876REVIEWSОБЗОР ЛИТЕРАТУРЫReview ArticleThe role of exosomes in the diagnostics and treatment of immune mediated skin disoders, wounds and alopeciaРоль экзосом в диагностике и лечении иммуноопосредованных дерматозов, лечении кожных ран и алопецииhttps://orcid.org/0000-0002-6801-3452P-1585-20157534-4443PalkinaNadezhda V.ПалкинаНадежда Владимировна
Russian Federation

MD, Dr. Sci. (Med.), Professor

д.м.н., профессор

mosmannv@yandex.ruZenaishviliRevaz D.ЗенаишвилиРеваз Дмитриевич
Russian Federation

PhD, Student

аспирант

ya.zrevaz@yandex.ruhttps://orcid.org/0000-0001-8142-42835412-2148RukshaTatiana G.РукшаТатьяна Геннадьевна
Russian Federation

MD, Dr. Sci. (Med.), Professor

д.м.н., профессор

tatyana_ruksha@mail.ruProf. V.F. Voino-Yasenetsky Krasnoyarsk State Medical UniversityКрасноярский государственный медицинский университет имени профессора В.Ф. Войно-Ясенецкого170420242005202410028170506202313022024Copyright ©; 2024, Palkina N.V., Zenaishvili R.D., Ruksha T.G.Copyright ©; 2024, Палкина Н.В., Зенаишвили Р.Д., Рукша Т.Г.2024Palkina N.V., Zenaishvili R.D., Ruksha T.G.Палкина Н.В., Зенаишвили Р.Д., Рукша Т.Г.https://creativecommons.org/licenses/by-nc/4.0https://vestnikdv.ru/jour/article/view/11876

Exosomes are microvesicles secreted by different cells that have the specificity and ability to transfer their cargo, including various regulatory molecules, to other cells. Exosomes cargo analysis considered to be a promising approach for diagnostics and therapeutic agents delivery into cells. Molecules derived from exosome cargo supposed to be plausible diagnostics criteria. This review provides up-to-date information on the exosomes origin and composition followed by a description of their diagnostic potential. New data summarized on the possibilities of exosomes application for the treatment of chronic immune-mediated cutaneous disorders, alopecia and cutaneous wound healing.

Экзосомы представляют собой микровезикулы, выделяемые практически всеми клетками организма и обладающие специфичностью и способностью передавать свое содержимое, включая разнообразные регуляторные молекулы, в другие клетки. Анализ экзосом — перспективное направление биомедицинских исследований, включающее выявление содержимого экзосом в целях диагностики, их использование в качестве средств доставки терапевтических агентов. Предполагается, что молекулы, составляющие содержимое экзосом, могут быть применены в качестве дифференциальных критериев при различных заболеваниях. В данном обзоре представлена актуальная информация о происхождении и составе экзосом, описывается их диагностический потенциал. Приведены новые сведения о возможностях использования экзосом в терапии хронических иммуноопосредованных дерматозов, патологии волос и при заживлении кожных ран.

exosomespsoriasisatopic dermatitiswound healingalopeciatargeted therapyэкзосомыпсориазатопический дерматитзаживление раналопециятаргетная терапияKarimi N, Ali Hosseinpour Feizi M, Safaralizadeh R, et al. Serum overexpression of miR-301a and miR-23a in patients with colorectal cancer. J Chin Med Assoc. 2019;82(3):215–220. doi: 10.1097/JCMA.0000000000000031Fu F, Jiang W, Zhou L, Chen Z. Circulating Exosomal miR-17-5p and miR-92a-3p Predict Pathologic Stage and Grade of Colorectal Cancer. Transl Oncol. 2018;11(2):221–232. doi: 10.1016/j.tranon.2017.12.012Li J, Xue H, Li T, Chu X, Xin D, Xiong Y, et al. Exosomes derived from mesenchymal stem cells attenuate the progression of atherosclerosis in ApoE-/- mice via miR-let7 mediated infiltration and polarization of M2 macrophage. Biochem Biophys Res Commun. 2019;510(4):565–572. doi: 10.1016/j.bbrc.2019.02.005Khare D, Or R, Resnick I, Barkatz C, Almogi-Hazan O, Avni B. Mesenchymal Stromal Cell-Derived Exosomes Affect mRNA Expression and Function of B-Lymphocytes. Front Immunol. 2018;9:3053. doi: 10.3389/fimmu.2018.03053Hu W, Song X, Yu H, Sun J, Zhao Y. Released Exosomes Contribute to the Immune Modulation of Cord Blood-Derived Stem Cells. Front Immunol. 2020;11:165. doi: 10.3389/fimmu.2020.00165PubMed Central. National Library of Medicine. URL: https://pubmed.ncbi.nlm.nih.gov/ (аccessed: 01.02.2004).Kalluri R, LeBleu VS. The biology, function, and biomedical applications of exosomes. Science. 2020;367(6478):eaau6977. doi: 10.1126/science.aau6977Trams EG, Lauter CJ, Salem N Jr, Heine U. Exfoliation of membrane ecto-enzymes in the form of micro-vesicles. Biochim Biophys Acta. 1981;645(1):63–70. doi: 10.1016/0005-2736(81)90512-5Guo S, Zhao L, Tao S, Zhang C. [Research progress on the role of extracellular vesicles in bacterial pathogenesis]. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2018;32(12):1597–1604. Chinese. doi: 10.7507/1002-1892.201805075Danesh A, Inglis HC, Jackman RP, Wu S, Deng X, Muench MO, et al. Exosomes from red blood cell units bind to monocytes and induce proinflammatory cytokines, boosting T-cell responses in vitro. Blood. 2014;123(5):687–696. doi: 10.1182/blood-2013-10-530469Aatonen MT, Ohman T, Nyman TA, Laitinen S, Grönholm M, Siljander PR. Isolation and characterization of platelet-derived extracellular vesicles. J Extracell Vesicles. 2014;3. doi: 10.3402/jev.v3.24692Yu X, Huang C, Song B, Xiao Y, Fang M, Feng J, et al. CD4+CD25+ regulatory T cells-derived exosomes prolonged kidney allograft survival in a rat model. Cell Immunol. 2013;285(1–2):62–68. doi: 10.1016/j.cellimm.2013.06.010Luga V, Wrana JL. Tumor-stroma interaction: Revealing fibroblast-secreted exosomes as potent regulators of Wnt-planar cell polarity signaling in cancer metastasis. Cancer Res. 2013;73(23):6843–6847. doi: 10.1158/0008-5472.CAN-13-1791Ju R, Zhuang ZW, Zhang J, Lanahan AA, Kyriakides T, Sessa WC, et al. Angiopoietin-2 secretion by endothelial cell exosomes: regulation by the phosphatidylinositol 3-kinase (PI3K)/Akt/endothelial nitric oxide synthase (eNOS) and syndecan-4/syntenin pathways. J Biol Chem. 2014;289(1):510–519. doi: 10.1074/jbc.M113.506899Kim SM, Yang Y, Oh SJ, Hong Y, Seo M, Jang M. Cancer-derived exosomes as a delivery platform of CRISPR/Cas9 confer cancer cell tropism-dependent targeting. J Control Release. 2017;266:8–16. doi: 10.1016/j.jconrel.2017.09.013Kharaziha P, Ceder S, Li Q, Panaretakis T. Tumor cell-derived exosomes: a message in a bottle. Biochim Biophys Acta. 2012;1826(1):103–111. doi: 10.1016/j.bbcan.2012.03.006Tiwari A, Singh A, Verma S, Stephenson S, Bhowmick T, Sangwan VS. Mini Review: Current Trends and Understanding of Exosome Therapeutic Potential in Corneal Diseases. Front Pharmacol. 2021;12:684712. doi: 10.3389/fphar.2021.684712Buschow SI, Liefhebber JM, Wubbolts R, Stoorvogel W. Exosomes contain ubiquitinated proteins. Blood Cells Mol Dis. 2005;35(3):398–403. doi: 10.1016/j.bcmd.2005.08.005Yuan X, Bhat OM, Lohner H, Zhang Y, Li PL. Endothelial acid ceramidase in exosome-mediated release of NLRP3 inflammasome products during hyperglycemia: Evidence from endothelium-specific deletion of Asah1 gene. Biochim Biophys Acta Mol Cell Biol Lipids. 2019;1864(12):158532. doi: 10.1016/j.bbalip.2019.158532Zhang H, Freitas D, Kim HS, Fabijanic K, Li Z, Chen H, et al. Identification of distinct nanoparticles and subsets of extracellular vesicles by asymmetric flow field-flow fractionation. Nat Cell Biol. 2018;20(3):332–343. doi: 10.1038/s41556-018-0040-4Fu M, Gu J, Jiang P, Qian H, Xu W, Zhang X. Exosomes in gastric cancer: roles, mechanisms, and applications. Mol Cancer. 2019;18(1):41. doi: 10.1186/s12943-019-1001-7Aksenenko MB, Palkina NV, Sergeeva ON, Sergeeva EYu, Kirichenko AK, Ruksha TG. miR-155 overexpression is followed by downregulation of its target gene, NFE2L2, and altered pattern of VEGFA expression in the liver of melanoma B16-bearing mice at the premetastatic stage. Int J Exp Pathol. 2019;100(5–6):311–319. doi: 10.1111/iep.12342Segura MF, Hanniford D, Menendez S, Reavie L, Zou X, Alvarez-Diaz S, et al. Aberrant miR-182 expression promotes melanoma metastasis by repressing FOXO3 and microphthalmia-associated transcription factor. Proc Natl Acad Sci U S A. 2009;106(6):1814–1819. doi: 10.1073/pnas.0808263106Conde-Vancells J, Rodriguez-Suarez E, Embade N, Gil D, Matthiesen R, Valle M, et al. Characterization and comprehensive proteome profiling of exosomes secreted by hepatocytes. J Proteome Res. 2008;7(12):5157–5166. doi: 10.1021/pr8004887Lo Cicero A, Delevoye C, Gilles-Marsens F, Loew D, Dingli F, Guéré C, et al. Exosomes released by keratinocytes modulate melanocyte pigmentation. Nat Commun. 2015;6:7506. doi: 10.1038/ncomms8506Khan AQ, Akhtar S, Prabhu KS, Zarif L, Khan R, Alam M, et al. Exosomes: Emerging Diagnostic and Therapeutic Targets in Cutaneous Diseases. Int J Mol Sci. 2020;21(23):9264. doi: 10.3390/ijms21239264Wang X, Tian L, Lu J, Ng IO. Exosomes and cancer — Diagnostic and prognostic biomarkers and therapeutic vehicle. Oncogenesis. 2022;11(1):54. doi: 10.1038/s41389-022-00431-5Oba R, Isomura M, Igarashi A, Nagata K. Circulating CD3+HLA-DR+ Extracellular Vesicles as a Marker for Th1/Tc1-Type Immune Responses. J Immunol Res. 2019;2019:6720819. doi: 10.1155/2019/6720819Chen XM, Zhao Y, Wu XD, Wang MJ, Yu H, Lu JJ, et al. Novel findings from determination of common expressed plasma exosomal microRNAs in patients with psoriatic arthritis, psoriasis vulgaris, rheumatoid arthritis, and gouty arthritis. Discov Med. 2019;28(151):47–68.Chen C, Wang D, Moshaverinia A, Liu D, Kou X, Yu W, et al. Mesenchymal stem cell transplantation in tight-skin mice identifies miR-151-5p as a therapeutic target for systemic sclerosis. Cell Res. 2017;27(4):559–577. doi: 10.1038/cr.2017.11Shi H, Wang M, Sun Y, Yang D, Xu W, Qian H. Exosomes: Emerging Cell-Free Based Therapeutics in Dermatologic Diseases. Front Cell Dev Biol. 2021;9:736022. doi: 10.3389/fcell.2021.736022Jiang M, Fang H, Shao S, Dang E, Zhang J, Qiao P, et al. Keratinocyte exosomes activate neutrophils and enhance skin inflammation in psoriasis. FASEB J. 2019;33(12):13241–13253. doi: 10.1096/fj.201900642RPaolino G, Buratta S, Mercuri SR, Pellegrino RM, Urbanelli L, Emiliani C, et al. Lipidic Profile Changes in Exosomes and Microvesicles Derived From Plasma of Monoclonal Antibody-Treated Psoriatic Patients. Front Cell Dev Biol. 2022;10:923769. doi: 10.3389/fcell.2022.923769Colletti M, Galardi A, De Santis M, Guidelli GM, Di Giannatale A, Di Luigi L, et al. Exosomes in Systemic Sclerosis: Messengers Between Immune, Vascular and Fibrotic Components? Int J Mol Sci. 2019;20(18):4337. doi: 10.3390/ijms20184337Zhu T, Wang Y, Jin H, Li L. The role of exosome in autoimmune connective tissue disease. Ann Med. 2019;51(2):101–108. doi: 10.1080/07853890.2019.1592215Nasiri Kenari A, Cheng L, Hill AF. Methods for loading therapeutics into extracellular vesicles and generating extracellular vesicles mimetic-nanovesicles. Methods. 2020;177:103–113. doi: 10.1016/j.ymeth.2020.01.001Tao SC, Guo SC, Li M, Ke QF, Guo YP, Zhang CQ. Chitosan Wound Dressings Incorporating Exosomes Derived from MicroRNA-126-Overexpressing Synovium Mesenchymal Stem Cells Provide Sustained Release of Exosomes and Heal Full-Thickness Skin Defects in a Diabetic Rat Model. Stem Cells Transl Med. 2017;6(3):736–747. doi: 10.5966/sctm.2016-0275Liu W, Yu M, Xie D, Wang L, Ye C, Zhu Q, et al. Melatonin-stimulated MSC-derived exosomes improve diabetic wound healing through regulating macrophage M1 and M2 polarization by targeting the PTEN/AKT pathway. Stem Cell Res Ther. 2020;11(1):259. doi: 10.1186/s13287-020-01756-xBrennan MÁ, Layrolle P, Mooney DJ. Biomaterials functionalized with MSC secreted extracellular vesicles and soluble factors for tissue regeneration. Adv Funct Mater. 2020;30(37):1909125. doi: 10.1002/adfm.201909125Dainichi T, Hanakawa S, Kabashima K. Classification of inflammatory skin diseases: a proposal based on the disorders of the three-layered defense systems, barrier, innate immunity and acquired immunity. J Dermatol Sci. 2014;76(2):81–89. doi: 10.1016/j.jdermsci.2014.08.010Leung DY. New insights into atopic dermatitis: role of skin barrier and immune dysregulation. Allergol Int. 2013;62(2):151–161. doi: 10.2332/allergolint.13-RAI-0564Torres T, Ferreira EO, Gonçalo M, Mendes-Bastos P, Selores M, Filipe P. Update on Atopic Dermatitis. Acta Med Port. 2019;32(9):606–613. doi: 10.20344/amp.11963Shin 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(3):680. doi: 10.3390/cells9030680Cho 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(1):187. doi: 10.1186/s13287-018-0939-5Cheung KL, Jarrett R, Subramaniam S, Salimi M, Gutowska-Owsiak D, Chen YL, et al. Psoriatic T cells recognize neolipid antigens generated by mast cell phospholipase delivered by exosomes and presented by CD1a. J Exp Med. 2016;213(11):2399–2412. doi: 10.1084/jem.20160258Jacquin-Porretaz C, Cordonnier M, Nardin C, Boullerot L, Chanteloup G, Vautrot V, et al. Increased Levels of Interleukin-17A Exosomes in Psoriasis. Acta Derm Venereol. 2019;99(12):1143–1147. doi: 10.2340/00015555-3300Zhang Y, Yan J, Li Z, Zheng J, Sun Q. Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells Alleviate Psoriasis-like Skin Inflammation. J Interferon Cytokine Res. 2022;42(1):8–18. doi: 10.1089/jir.2021.0146Hu P, Yang Q, Wang Q, Shi C, Wang D, Armato U, et al. Mesenchymal stromal cells-exosomes: a promising cell-free therapeutic tool for wound healing and cutaneous regeneration. Burns Trauma. 2019;7:38. doi: 10.1186/s41038-019-0178-8Kim YJ, Yoo SM, Park HH, Lim HJ, Kim YL, Lee S, et al. Exosomes derived from human umbilical cord blood mesenchymal stem cells stimulates rejuvenation of human skin. Biochem Biophys Res Commun. 2017;493(2):1102–1108. doi: 10.1016/j.bbrc.2017.09.056Zhang B, Wang M, Gong A, Zhang X, Wu X, Zhu Y, et al. HucMSC-Exosome Mediated-Wnt4 Signaling Is Required for Cutaneous Wound Healing. Stem Cells. 2015;33(7):2158–2168. doi: 10.1002/stem.1771Fang S, Xu C, Zhang Y, Xue C, Yang C, Bi H, et al. Umbilical Cord-Derived Mesenchymal Stem Cell-Derived Exosomal MicroRNAs Suppress Myofibroblast Differentiation by Inhibiting the Transforming Growth Factor-β/SMAD2 Pathway During Wound Healing. Stem Cells Transl Med. 2016;5(10):1425–1439. doi: 10.5966/sctm.2015-0367Goodarzi P, Larijani B, Alavi-Moghadam S, Tayanloo-Beik A, Mohamadi-Jahani F, Ranjbaran N, et al. Mesenchymal Stem Cells-Derived Exosomes for Wound Regeneration. Adv Exp Med Biol. 2018;1119:119–131. doi: 10.1007/5584_2018_251Nawaz M, Fatima F, Vallabhaneni KC, Penfornis P, Valadi H, Ekström K, et al. Extracellular Vesicles: Evolving Factors in Stem Cell Biology. Stem Cells Int. 2016;2016:1073140. doi: 10.1155/2016/1073140Li X, Xie X, Lian W, Shi R, Han S, Zhang H, et al. Exosomes from adipose-derived stem cells overexpressing Nrf2 accelerate cutaneous wound healing by promoting vascularization in a diabetic foot ulcer rat model. Exp Mol Med. 2018;50(4):1–14. doi: 10.1038/s12276-018-0058-5Zhao B, Zhang Y, Han S, Zhang W, Zhou Q, Guan H, et al. Exosomes derived from human amniotic epithelial cells accelerate wound healing and inhibit scar formation. J Mol Histol. 2017;48(2):121–132. doi: 10.1007/s10735-017-9711-xMa T, Fu B, Yang X, Xiao Y, Pan M. Adipose mesenchymal stem cell-derived exosomes promote cell proliferation, migration, and inhibit cell apoptosis via Wnt/β-catenin signaling in cutaneous wound healing. J Cell Biochem. 2019;120(6):10847–10854. doi: 10.1002/jcb.28376Zhang W, Bai X, Zhao B, Li Y, Zhang Y, Li Z, et al. Cell-free therapy based on adipose tissue stem cell-derived exosomes promotes wound healing via the PI3K/Akt signaling pathway. Exp Cell Res. 2018;370(2):333–342. doi: 10.1016/j.yexcr.2018.06.035Wang X, Jiao Y, Pan Y, Zhang L, Gong H, Qi Y, et al. Fetal Dermal Mesenchymal Stem Cell-Derived Exosomes Accelerate Cutaneous Wound Healing by Activating Notch Signaling. Stem Cells Int. 2019;2019:2402916. doi: 10.1155/2019/2402916Fukuoka H, Narita K, Suga H. Hair Regeneration Therapy: Application of Adipose-Derived Stem Cells. Curr. Stem Cell Res Ther. 2017;12(7):531–534. doi: 10.2174/1574888X12666170522114307Zhou L, Wang H, Jing J, Yu L, Wu X, Lu Z. Regulation of hair follicle development by exosomes derived from dermal papilla cells. Biochem Biophys Res Commun. 2018;500(2):325–332. doi: 10.1016/j.bbrc.2018.04.067Ha DH, Kim HK, Lee J, Kwon HH, Park GH, Yang SH, et al. Mesenchymal Stem/Stromal Cell-Derived Exosomes for Immunomodulatory Therapeutics and Skin Regeneration. Cells. 2020;9(5):1157. doi: 10.3390/cells9051157Carrasco E, Soto-Heredero G, Mittelbrunn M. The Role of Extracellular Vesicles in Cutaneous Remodeling and Hair Follicle Dynamics. Int J Mol Sci. 2019;20(11):2758. doi: 10.3390/ijms20112758