Consilium MedicumConsilium MedicumConsilium MedicumConsilium Medicum2075-17532542-2170Consilium Medicum35256710.26442/20751753.2024.9.202668ArticlesСтатьиReview ArticleTherapeutic potential of mesenchymal stem cells and stem cell-derived extracellular vesicles in tuberculosis of various localizations: A reviewТерапевтический потенциал мезенхимных стволовых клеток и выделенных из них внеклеточных везикул при туберкулезе различных локализацийhttps://orcid.org/0009-0008-6843-1145ShumkoVeronika V.ШумкоВероника Викторовна
Russian Federation

Intern

стажер, студентка мед. фак-та

ivanova.yana803@gmail.comhttps://orcid.org/0000-0002-2858-5317GorelovAndrei I.ГореловАндрей Игоревич
Russian Federation

D. Sci. (Med.), Prof.

д-р мед. наук, проф., проф. каф. госпитальной хирургии мед. фак-та

ivanova.yana803@gmail.comhttps://orcid.org/0000-0001-8145-4159RemezovaAnna N.РемезоваАнна Николаевна

Graduate Student, Res. Assist.

аспирант, мл. науч. сотр.

ivanova.yana803@gmail.comhttps://orcid.org/0000-0002-4885-8095IvanovaYanina G.ИвановаЯнина Георгиевна
Russian Federation

Resident

ординатор каф. госпитальной хирургии мед. фак-та

ivanova.yana803@gmail.comhttps://orcid.org/0000-0002-6974-5305MuraviovAlexandr N.МуравьевАлександр Николаевич
Russian Federation

Cand. Sci. (Med.)

канд. мед. наук, ученый секретарь, доц. каф. хирургических болезней

ivanova.yana803@gmail.comhttps://orcid.org/0000-0002-7357-1571YudintcevaNatalia M.ЮдинцеваНаталия Михайловна
Russian Federation

Cand. Sci. (Biol.)

канд. биол. наук, ст. науч. сотр.

ivanova.yana803@gmail.comhttps://orcid.org/0000-0002-5234-349XVinogradovaTatiana I.ВиноградоваТатьяна Ивановна
Russian Federation

D. Sci. (Med.), Prof.

д-р мед. наук, проф., вед. науч. сотр.

ivanova.yana803@gmail.comhttps://orcid.org/0000-0002-7010-7562GorelovaAnna A.ГореловаАнна Андреевна
Russian Federation

Senior Res. Officer, Assoc. Prof.

ст. науч. сотр., доц. каф. госпитальной хирургии мед. фак-та

ivanova.yana803@gmail.comSaint Petersburg State Research Institute of PhthisiopulmonologyФГБУ «Санкт-Петербургский научно-исследовательский институт фтизиопульмонологии» Минздрава РоссииSaint Petersburg State UniversityФГБОУ ВО «Санкт-Петербургский государственный университет»Saint Petersburg Medico-Social InstituteЧОУ ВО «Санкт-Петербургский медико-социальный институт»Institute of Cytology of the Russian Academy of SciencesФГБУН «Институт цитологии Российской академии наук»13102024269Otorhinolaryngology and pulmonologyОториноларингология и пульмонология6116142804202318092023Copyright ©; 2024, Consilium MedicumCopyright ©; 2024, ООО "Консилиум Медикум"2024Consilium MedicumООО "Консилиум Медикум"https://creativecommons.org/licenses/by-nc-sa/4.0https://consilium.orscience.ru/2075-1753/article/view/352567

Experimental and clinical studies using cell therapy are very popular. Mesenchymal stem cells (MSCs) and stem cell-derived extracellular vesicles (EV) are used as one of the components of therapy in these researches. The action of MSCs is mediated by the release of EV which play a direct role in the implementation of several important biological processes: angiogenesis, proliferation, modulation of the inflammatory process and immune response, inhibition of cellular apoptosis, etc. These properties of MSCs and stem cell-derived EV are of interest in the treatment of tuberculosis infection, because an integral part of the pathogenesis of tuberculosis is the creation of specific granulomas and the formation of fibrosis.

Экспериментальные и клинические исследования с применением клеточной терапии, в которой мезенхимные стволовые клетки (МСК) и их производные – внеклеточные везикулы (ВВ) – применяют как один из компонентов лечения, пользуются большой популярностью. Действие МСК опосредовано выделением ВВ, которые играют непосредственную роль в осуществлении нескольких важных биологических процессов, таких как ангиогенез, клеточная пролиферация, модуляция воспалительного процесса и иммунного ответа, ингибирование клеточного апоптоза и др. Описанные свойства МСК и ВВ, выделенных из МСК, представляют интерес в лечении туберкулезной инфекции, неотъемлемую часть патогенеза которой составляют формирование специфических гранулем и образование фиброза.

tuberculosisextracellular vesiclesmesenchymal stem cellsтуберкулезвнеклеточные везикулымезенхимные стволовые клеткиHonmou O, Yamashita T, Morita T, et al. Intravenous infusion of auto serum-expanded autologous mesenchymal stem cells in spinal cord injury patients: 13 case series. Clin Neurol Neurosurg. 2021;203:106565. DOI:10.1016/j.clineuro.2021.106565Nakazaki M, Morita T, Lankford KL, et al. Small extracellular vesicles released by infused mesenchymal stromal cells target M2 macrophages and promote TGF-β upregulation, microvascular stabilization and functional recovery in a rodent model of severe spinal cord injury. J Extracell Vesicles. 2021;10(11):e12137. DOI:10.1002/jev2.12137Ahn SY, Sung DK, Kim YE, et al. Brain-derived neurotropic factor mediates neuroprotection of mesenchymal stem cell-derived extracellular vesicles against severe intraventricular hemorrhage in newborn rats. Stem Cells Transl Med. 2021;10(3):374-84. DOI:10.1002/sctm.20-0301Warnecke A, Harre J, Staecker H, et al. Extracellular vesicles from human multipotent stromal cells protect against hearing loss after noise trauma in vivo. Clin Transl Med. 2020;10(8):e262. DOI:10.1002/ctm2.262Balbi C, Vassalli G. Exosomes: Beyond stem cells for cardiac protection and repair. Stem Cells. 2020;38(11):1387-99. DOI:10.1002/stem.3261Loyer X, Zlatanova I, Devue C, et al. Intra-Cardiac Release of Extracellular Vesicles Shapes Inflammation Following Myocardial Infarction. Circ Res. 2018;123(1):100-6. DOI:10.1161/CIRCRESAHA.117.311326Cheng M, Yang J, Zhao X, et al. Circulating myocardial microRNAs from infarcted hearts are carried in exosomes and mobilise bone marrow progenitor cells. Nat Commun. 2019;10(1):959. DOI:10.1038/s41467-019-08895-7Mayourian J, Cashman TJ, Ceholski DK, et al. Experimental and Computational Insight Into Human Mesenchymal Stem Cell Paracrine Signaling and Heterocellular Coupling Effects on Cardiac Contractility and Arrhythmogenicity. Circ Res. 2017;121(4):411-23. DOI:10.1161/CIRCRESAHA.117.310796Gelberman RH, Linderman SW, Jayaram R, et al. Combined Administration of ASCs and BMP-12 Promotes an M2 Macrophage Phenotype and Enhances Tendon Healing. Clin Orthop Relat Res. 2017;475(9):2318-31. DOI:10.1007/s11999-017-5369-7Shen H, Yoneda S, Abu-Amer Y, et al. Stem cell-derived extracellular vesicles attenuate the early inflammatory response after tendon injury and repair. J Orthop Res. 2020;38(1):117-27. DOI:10.1002/jor.24406Zhang S, Chuah SJ, Lai RC, et al. MSC exosomes mediate cartilage repair by enhancing proliferation, attenuating apoptosis and modulating immune reactivity. Biomaterials. 2018;156:16-27. DOI:10.1016/j.biomaterials.2017.11.028Woo CH, Kim HK, Jung GY, et al. Small extracellular vesicles from human adipose-derived stem cells attenuate cartilage degeneration. J Extracell Vesicles. 2020;9(1):1735249. DOI:10.1080/20013078.2020.1735249Zheng J, Wang Q, Leng W, et al. Bone marrow derived mesenchymal stem cell conditioned medium attenuates tubulointerstitial fibrosis by inhibiting monocyte mobilization in an irreversible model of unilateral ureteral obstruction. Mol Med Rep. 2018;17(6):7701-7. DOI:10.3892/mmr.2018.8848Орлова Н.В., Муравьев А.Н., Виноградова Т.И., и др. Клеточные технологии в реконструктивной хирургии мочевого пузыря. Медицинский Альянс. 2015;(1):149 [Orlova NV, Muraviev AN, Vinogradova TI, et al. Kletochnye tekhnologii v rekonstruktivnoi khirurgii mochevogo puzyria. Meditsinskii Al'ians. 2015;(1):149 (in Russian)].Grange C, Tritta S, Tapparo M, et al. Stem cell-derived extracellular vesicles inhibit and revert fibrosis progression in a mouse model of diabetic nephropathy. Sci Rep. 2019;9(1):4468. DOI:10.1038/s41598-019-41100-9He J, Wang Y, Sun S, et al. Bone marrow stem cells-derived microvesicles protect against renal injury in the mouse remnant kidney model. Nephrology (Carlton). 2012;17(5):493-500. DOI:10.1111/j.1440-1797.2012.01589.xГусейнова Ф.М., Виноградова Т.И., Заболотных Н.В., и др. Влияние клеточной терапии мезенхимными клетками стромы костного мозга на процессы репарации при экспериментальном туберкулезном сальпингите. Медицинский Альянс. 2017;(3):35-44 [Guseinova FM, Vinogradova TI, Zabolotnykh NV, et al. The impact of cellular therapy with mesenchymal stem cells of bone marrow on reparation at experimental tuberculous salpingitis. Meditsinskii Al'ians. 2020;(4):35-44 (in Russian)].Eirin A, Zhu XY, Puranik AS, et al. Mesenchymal stem cell-derived extracellular vesicles attenuate kidney inflammation. Kidney Int. 2017;92(1):114-24. DOI:10.1016/j.kint.2016.12.023Bruno S, Chiabotto G, Favaro E, et al. Role of extracellular vesicles in stem cell biology. Am J Physiol Cell Physiol. 2019;317(2):C303-13. DOI:10.1152/ajpcell.00129.2019Yuan QL, Zhang YG, Chen Q. Mesenchymal Stem Cell (MSC)-Derived Extracellular Vesicles: Potential Therapeutics as MSC Trophic Mediators in Regenerative Medicine. Anat Rec (Hoboken). 2020;303(6):1735-42. DOI:10.1002/ar.24186Bohlbro AS, Hvingelby VS, Rudolf F, et al. Active case-finding of tuberculosis in general populations and at-risk groups: a systematic review and meta-analysis. Eur Respir J. 2021;58(4). DOI:10.1183/13993003.00090-2021Muneer A, Macrae B, Krishnamoorthy S, Zumla A. Urogenital tuberculosis – epidemiology, pathogenesis and clinical features. Nat Rev Urol. 2019;16(10):573-98. DOI:10.1038/s41585-019-0228-9Furin J, Cox H, Pai M. Tuberculosis. Lancet. 2019;393(10181):1642-56. DOI:10.1016/S0140-6736(19)30308-3Hur YH, Cerione RA, Antonyak MA. Extracellular vesicles and their roles in stem cell biology. Stem Cells. 2020;38(4):469-76. DOI:10.1002/stem.3140Bruno S, Tapparo M, Collino F, et al. Renal Regenerative Potential of Different Extracellular Vesicle Populations Derived from Bone Marrow Mesenchymal Stromal Cells. Tissue Eng Part A. 2017;23(21-22):1262-73. DOI:10.1089/ten.TEA.2017.0069Baek G, Choi H, Kim Y, et al. Mesenchymal Stem Cell-Derived Extracellular Vesicles as Therapeutics and as a Drug Delivery Platform. Stem Cells Transl Med. 2019;8(9):880-6. DOI:10.1002/sctm.18-0226Marar C, Starich B, Wirtz D. Extracellular vesicles in immunomodulation and tumor progression. Nat Immunol. 2021;22(5):560-70. DOI:10.1038/s41590-021-00899-0Harrell CR, Jovicic N, Djonov V, et al. Mesenchymal Stem Cell-Derived Exosomes and Other Extracellular Vesicles as New Remedies in the Therapy of Inflammatory Diseases. Cells. 2019;8(12). DOI:10.3390/cells8121605Joshi L, Chelluri LK, Gaddam S. Mesenchymal Stromal Cell Therapy in MDR/XDR Tuberculosis: A Concise Review. Arch Immunol Ther Exp (Warsz). 2015;63(6):427-33. DOI:10.1007/s00005-015-0347-9Yates AG, Pink RC, Erdbrügger U, et al. In sickness and in health: The functional role of extracellular vesicles in physiology and pathology in vivo: Part II: Pathology: Part II: Pathology. J Extracell Vesicles. 2022;11(1):e12190. DOI:10.1002/jev2.12190Guo H, Su Y, Deng F. Effects of Mesenchymal Stromal Cell-Derived Extracellular Vesicles in Lung Diseases: Current Status and Future Perspectives. Stem Cell Rev Rep. 2021;17(2):440-58. DOI:10.1007/s12015-020-10085-8Tieu A, Hu K, Gnyra C, et al. Mesenchymal stromal cell extracellular vesicles as therapy for acute and chronic respiratory diseases: A meta-analysis. J Extracell Vesicles. 2021;10(12):e12141. DOI:10.1002/jev2.12141Dinh PC, Paudel D, Brochu H, et al. Inhalation of lung spheroid cell secretome and exosomes promotes lung repair in pulmonary fibrosis. Nat Commun. 2020;11(1):1064. DOI:10.1038/s41467-020-14344-7Maremanda KP, Sundar IK, Rahman I. Protective role of mesenchymal stem cells and mesenchymal stem cell-derived exosomes in cigarette smoke-induced mitochondrial dysfunction in mice. Toxicol Appl Pharmacol. 2019;385:114788. DOI:10.1016/j.taap.2019.114788Schwartz YS, Belogorodtsev SN, Filimonov PN, et al. BCG infection in mice is promoted by naïve mesenchymal stromal cells (MSC) and suppressed by poly(A:U)-conditioned MSC. Tuberculosis (Edinb). 2016;101:130-6. DOI:10.1016/j.tube.2016.09.005Nenasheva T, Nikolaev A, Diykanov D, et al. The introduction of mesenchymal stromal cells induces different immunological responses in the lungs of healthy and M. tuberculosis infected mice. PLoS One. 2017;12(6):e0178983. DOI:10.1371/journal.pone.0178983Jain N, Kalam H, Singh L, et al. Mesenchymal stem cells offer a drug-tolerant and immune-privileged niche to Mycobacterium tuberculosis. Nat Commun. 2020;11(1):3062. DOI:10.1038/s41467-020-16877-3Aqdas M, Singh S, Amir M, et al. Cumulative Signaling Through NOD-2 and TLR-4 Eliminates the Mycobacterium Tuberculosis Concealed Inside the Mesenchymal Stem Cells. Front Cell Infect Microbiol. 2021;11:669168. DOI:10.3389/fcimb.2021.669168Taghavi-Farahabadi M, Mahmoudi M, Mahdaviani SA, et al. Improving the function of neutrophils from chronic granulomatous disease patients using mesenchymal stem cells' exosomes. Hum Immunol. 2020;81(10-11):614-24. DOI:10.1016/j.humimm.2020.05.009Ерохин В.В., Васильева И.А, Коноплянников А.Г., и др. Системная трансплантация аутологичных мезенхимальных стволовых клеток костного мозга в лечении больных множественным лекарственно-устойчивым туберкулезом легких. Проблемы туберкулеза и болезней легких. 2008;(10):3-6 [Erokhin VV, Vasil'eva IA, Konopliannikov AG, et al. Systemic transplantation of autologous mesenchymal stem cells of the bone marrow in the treatment of patients with multidrug-resistant pulmonary tuberculosis. Probl Tuberk Bolezn Legk. 2008;(10):3-6 (in Russian)].Parida SK, Madansein R, Singh N, et al. Cellular therapy in tuberculosis. Int J Infect Dis. 2015;32:32-8. DOI:10.1016/j.ijid.2015.01.016Skrahin A, Ahmed RK, Ferrara G, et al. Autologous mesenchymal stromal cell infusion as adjunct treatment in patients with multidrug and extensively drug-resistant tuberculosis: an open-label phase 1 safety trial. Lancet Respir Med. 2014;2(2):108-22. DOI:10.1016/S2213-2600(13)70234-0Skrahin A, Jenkins HE, Hurevich H, et al. Effectiveness of a novel cellular therapy to treat multidrug-resistant tuberculosis. J Clin Tuberc Other Mycobact Dis. 2016;4:21-7. DOI:10.1016/j.jctube.2016.05.003Yan K, Xu G, Li Z. MicroRNA-20b carried by mesenchymal stem cell-derived extracellular vesicles protects alveolar epithelial type II cells from Mycobacterium tuberculosis infection in vitro. Infect Genet Evol. 2022;101:105292. DOI:10.1016/j.meegid.2022.105292Муравьев А.Н., Орлова Н.В., Горелова А.А., и др. Возможности тканевой инженерии и клеточных технологий в коррекции патологии органов мочевыделительной системы: анализ литературы и собственный опыт. Медицинский Альянс. 2022;10(4):79-86 [Muraviev AN, Orlova NV, Gorelova AA, et al. Tissue engineering and cell technologies: how these can help in correction of urinary system pathologies. Literature review and own experience. Meditsinskii Al'ians. 2022; 10(4):79-86 (in Russian)].Muraviov AN, Vinogradova TI, Remezova AN, et al. The Use of Mesenchymal Stem Cells in the Complex Treatment of Kidney Tuberculosis (Experimental Study). Biomedicines. 2022;10(12):3062. DOI:10.3390/biomedicines10123062Li H, Ding Y, Huang J, et al. Angiopep-2 Modified Exosomes Load Rifampicin with Potential for Treating Central Nervous System Tuberculosis. Int J Nanomedicine. 2023;18:489-503. DOI:10.2147/IJN.S395246Mehaffy C, Kruh-Garcia NA, Graham B, et al. Identification of Mycobacterium tuberculosis Peptides in Serum Extracellular Vesicles from Persons with Latent Tuberculosis Infection. J Clin Microbiol. 2020;58(6). DOI:10.1128/JCM.00393-20Lu G, Jiang X, Wu A, et al. Two Small Extracellular Vesicle sRNAs Derived From Mycobacterium tuberculosis Serve as Diagnostic Biomarkers for Active Pulmonary Tuberculosis. Front Microbiol. 2021;12:642559. DOI:10.3389/fmicb.2021.642559Mohammadzadeh R, Ghazvini K, Farsiani H, Soleimanpour S. Mycobacterium tuberculosis extracellular vesicles: exploitation for vaccine technology and diagnostic methods. Crit Rev Microbiol. 2021;47(1):13-33. DOI:10.1080/1040841X.2020.1830749Mehaffy C, Ryan JM, Kruh-Garcia NA, Dobos KM. Extracellular Vesicles in Mycobacteria and Tuberculosis. Front Cell Infect Microbiol. 2022;12:912831. DOI:10.3389/fcimb.2022.912831Sun YF, Pi J, Xu JF. Emerging Role of Exosomes in Tuberculosis: From Immunity Regulations to Vaccine and Immunotherapy. Front Immunol. 2021;12:628973. DOI:10.3389/fimmu.2021.628973