Genes & CellsGenes & CellsГены и КлеткиGenes and Cells2313-18292500-2562Human Stem Cells Institute69628910.17816/gc696289ACHTHZReviewsНаучные обзорыReview ArticleProspects for the use of mesenchymal stromal cells in the treatment of dilated cardiomyopathyПерспективы применения мезенхимных стромальных клеток в лечении дилатационной кардиомиопатииhttps://orcid.org/0009-0000-8229-01846987-6342MirzezadeZekhra E.МирзезадеЗехра Эльчин кызы
Russian Federation
zehra.mirzezade2006@gmail.comhttps://orcid.org/0000-0001-8467-06233854-7256PayushinaOlga V.ПаюшинаОльга Викторовна
Russian Federation

Dr. Sci. (Biology), Associate Professor

д-р биол. наук, доцент

payushina@mail.ruhttps://orcid.org/0000-0002-1381-02004644-5171TsomartovaDibakhan A.ЦомартоваДибахан Асланбековна
Russian Federation

MD, Dr. Sci. (Medicine), Associate Professor

д-р мед. наук, доцент

dtsomartova@mail.ruhttps://orcid.org/0000-0002-1046-63365567-4358ChereshnevaYelizaveta V.ЧерешневаEлизавета Васильевна
Russian Federation

MD, Cand. Sci. (Medicine), Associate Professor

канд. мед. наук, доцент

yelizaveta.new@mail.ruhttps://orcid.org/0000-0003-4648-90278123-7801KartashkinaNataliya L.КарташкинаНаталия Левоновна
Russian Federation

MD, Cand. Sci. (Medicine), Associate Professor

канд. мед. наук, доцент

knlmma@mail.ruhttps://orcid.org/0000-0002-8581-338X8957-3308TsomartovaElina S.ЦомартоваЭлина Сослановна
Russian Federation

MD, Cand. Sci. (Medicine)

канд. мед. наук

elina.tsomartova@gmail.comhttps://orcid.org/0000-0002-5484-95742589-3752KosobutskayaSvetlana A.КособуцкаяСветлана Александровна
Russian Federation

MD, Cand. Sci. (Medicine)

канд. мед. наук

fotinia78@mail.ruThe First Sechenov Moscow State Medical UniversityПервый Московский государственный медицинский университет имени И.М. Сеченова10032026270320262115161711202506022026Copyright ©; 2026, Eco-VectorCopyright ©; 2026, Эко-Вектор2026Eco-VectorЭко-Векторhttps://eco-vector.com/for_authors.php#07https://genescells.ru/2313-1829/article/view/696289

This review discusses the mechanisms underlying the therapeutic effects and the clinical prospects of mesenchymal stromal cell (MSC) transplantation in dilated cardiomyopathy. The development of dilated cardiomyopathy is based on a complex interplay of multiple etiological factors and mechanisms. This condition is characterized by high prevalence, unfavorable prognosis, and substantial mortality, highlighting the need for innovative treatment methods. In dilated cardiomyopathy, mesenchymal stromal cells exert multifaceted effects on the injured myocardium, primarily through paracrine secretion of cytoprotective, immunomodulatory, proangiogenic, and antifibrotic factors; suppression of oxidative stress; and restoration of cardiomyocyte energy metabolism. Preclinical and clinical studies have demonstrated the ability of mesenchymal stromal cells to improve cardiac contractile function and patients’ quality of life. Sustained long-term benefits have been reported, with allogeneic cells showing greater therapeutic potential and a lower incidence of complications compared with autologous cells. To enhance the efficacy of MSC transplantation and facilitate its broader implementation in clinical practice, several challenges must be addressed, including optimization of cell sources, delivery methods, and strategies to improve cell survival within the hostile myocardial microenvironment. In this context, genetic modification of mesenchymal stromal cells aimed at enhancing their cardioprotective and regenerative properties represents a promising approach to improving outcomes in patients with dilated cardiomyopathy.

В обзоре рассмотрены механизмы терапевтического действия и перспективы клинического использования трансплантации мезенхимных стромальных клеток (МСК) при дилатационной кардиомиопатии. В основе развития дилатационной кардиомиопатии лежит сложное взаимодействие множества причин и механизмов. Она характеризуется широкой распространённостью, неблагоприятным прогнозом и значительной смертностью, что обусловливает необходимость разработки инновационных методов лечения. МСК при этом заболевании способны оказывать комплексное влияние на повреждённый миокард, главным образом за счёт паракринной продукции цитопротективных, иммуномодулирующих, проангиогенных и антифибротических факторов, подавления окислительного стресса и восстановления энергетического обмена кардиомиоцитов. Результаты доклинических и клинических исследований подтверждают способность МСК улучшать сократительную функцию сердца и качество жизни пациентов. Отмечается долгосрочное сохранение полученных улучшений, при этом аллогенные клетки демонстрируют более выраженный терапевтический потенциал и меньшую частоту осложнений, чем аутологичные. Для повышения эффективности трансплантации МСК и её широкого внедрения в клиническую практику необходимо решить ряд задач, включая оптимизацию источников клеток, способов их доставки и повышение выживаемости в неблагоприятном микроокружении. В этом контексте генетическая модификация МСК, направленная на усиление их кардиопротективных и прорегенеративных свойств, открывает перспективные возможности для улучшения результатов лечения дилатационной кардиомиопатии.

heartdilated cardiomyopathycell transplantationmesenchymal stromal cellsсердцедилатационная кардиомиопатиятрансплантация клетокмезенхимные стромальные клеткиWexler RK, Elton T, Pleister A, Feldman D. Cardiomyopathy: an overview. Am Fam Physician. 2009;79(9):778–784.Arbustini E, Narula N, Tavazzi L, et al. The MOGE(S) classification of cardiomyopathy for clinicians. J Am Coll Cardiol. 2014;64(3):304–318. doi: 10.1016/j.jacc.2014.05.027 EDN: UTWVVBElliott P, Andersson B, Arbustini E, et al. Classification of the cardiomyopathies: a position statement from the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur Heart J. 2008;29(2):270–276. doi: 10.1093/eurheartj/ehm342 EDN: INSFOLTrisvetova EL. Dilated cardiomyopathy: modern principles of diagnosis and treatment. In: Cardiomyopathies: modern methods of diagnosis and treatment: proceedings of the Republican Scientific and Practical Conference. Minsk: Belarusian State Medical University; 2016. P. 106–117. (In Russ.) EDN: YOLGYCKiselev AM, Reut LI, Klushina AA. Autoantibodies in pathogenesis of dilated cardiomyopathy. Bjulleten’ Federal’nogo Centra serdca, krovi i jendokrinologii im. V.A. Almazova. 2013;(1):12–16. EDN: PXAWILKruchko LC, Taub GS. Dilated cardiomyopathy. Lechebnoe delo: nauchno-prakticheskij terapevticheskij zhurnal. 2021;(2):5–12. (In Russ.)Skvorcov VV, Tumarenko AV, Odincov VV, Skvorcova EM. Current issues in the diagnosis and treatment of dilated cardiomyopathy (DCM). Medical Alphabet. 2010;1(4):50–53. (In Russ.) EDN: NDGLFLMaldonado VV, Patel NH, Smith EE, et al. Clinical utility of mesenchymal stem/stromal cells in regenerative medicine and cellular therapy. J Biol Eng. 2023;17(1):44. doi: 10.1186/s13036-023-00361-9 EDN: NTTBPMYuce K. The application of mesenchymal stem cells in different cardiovascular disorders: ways of administration, and the effectors. Stem Cell Rev Rep. 2024;20(7):1671–1691. doi: 10.1007/s12015-024-10765-9Ryabenko DV. Dilated cardiomyopathy: genetic and molecular aspects of disease development. Ukrainian Journal of Cardiology. 2010;(3):96–109. EDN: PIYHUQSaryeva OP, Kulida LV, Protsenko EV, Malysheva MV. Cardiomyopathy in children—clinical, genetic and morphological aspects. I.P. Pavlov Russian Medical Biological Herald. 2020;28(1):99–110. doi: 10.23888/PAVLOVJ202028199-110 EDN: NYACACSchultheiss HP, Fairweather D, Caforio ALP, et al. Dilated cardiomyopathy. Nat Rev Dis Primers. 2019;5(1):32. doi: 10.1038/s41572-019-0084-1 EDN: NYACACAndreeva LS, Khamnueva LYu, Shagun OV. The role of cytokines in the pathogenesis of diabetes mellitus. Siberian Medical Journal (Irkutsk). 2003;38(3):5–8. EDN: OVZJTLKvetnoy IM, Linkova NS, Pukhalskaya AE, et al. Inflammaging: Role in pathogenesis and molecular diagnostics of age-related dilated cardiomyopathy. Pathogenesis. 2021;19(2):67–72. doi: 10.25557/2310-0435.2021.02.67-72 EDN: RJZFZGGurevich MA. Pathogenesis and treatment of heart failure in dilated cardiomyopathy. Cardiovascular Therapy and Prevention. 2005;4(1):83–89. EDN: IXVZWFGigli M, Stolfo D, Merlo M, et al. Pathophysiology of dilated cardiomyopathy: from mechanisms to precision medicine. Nat Rev Cardiol. 2025;22(3):183–198. doi: 10.1038/s41569-024-01074-2 EDN: YKIEWWAn Y, Xu BT, Wan SR, et al. The role of oxidative stress in diabetes mellitus-induced vascular endothelial dysfunction. Cardiovasc Diabetol. 2023;22(1):237. doi: 10.1186/s12933-023-01965-7 EDN: QXWXHKCai H, Harrison DG. Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress. Circ Res. 2000;87(10):840–844. doi: 10.1161/01.res.87.10.840Reddy S, Eliassen E, Krueger GR, Das BB. Human herpesvirus 6-induced inflammatory cardiomyopathy in immunocompetent children. Ann Pediatr Cardiol. 2017;10(3):259–268. doi: 10.4103/apc.APC_54_17Chistyakova MV, Govorin AV, Mudrov VA, et al. Heart damage and endothelial dysfunction in patients with coronavirus infection. Vestnik terapevta. 2023;(1):3–16. EDN: UHZJWGRoura S, Bayes-Genis A. Vascular dysfunction in idiopathic dilated cardiomyopathy. Nat Rev Cardiol. 2009;6(9):590–598. doi: 10.1038/nrcardio.2009.130Sapin MR, Nikolenko VN, Milyukov VYe, et al. Morphological and functional organization of myocytes of atria and ventricles of the heart. Zhurnal anatomii i gistopatologii. 2012;1(1):11–17. EDN: PLNPVTRubiś P, Wiśniowska-Śmialek S, Wypasek E, et al. Fibrosis of extracellular matrix is related to the duration of the disease but is unrelated to the dynamics of collagen metabolism in dilated cardiomyopathy. Inflamm Res. 2016;65(12):941–949. doi: 10.1007/s00011-016-0977-3 EDN: JKKKGYMarijianowski MM, Teeling P, Mann J, Becker AE. Dilated cardiomyopathy is associated with an increase in the type I/type III collagen ratio: a quantitative assessment. J Am Coll Cardiol. 1995;25(6):1263–1272. doi: 10.1016/0735-1097(94)00557-7 EDN: APRYTTGomez-Salazar M, Gonzalez-Galofre ZN, Casamitjana J, et al. Five decades later, are mesenchymal stem cells still relevant? Front Bioeng Biotechnol. 2020;8:148. doi: 10.3389/fbioe.2020.00148 EDN: MXLKACPayushina OV, Tsomartova DA, Chereshneva EV, et al. Activation of endogenous mesenchymal stromal cells as an approach to tissue regeneration. Cell and Tissue Biology. 2023;17(4):328–338. doi: 10.1134/s1990519x23040065 EDN: CTJJDZSamsonraj RM, Raghunath M, Nurcombe V, et al. Concise review: multifaceted characterization of human mesenchymal stem cells for use in regenerative medicine. Stem Cells Transl Med. 2017;6(12):2173–2185. doi: 10.1002/sctm.17-0129 EDN: YKBBIMHare JM, DiFede DL, Rieger AC, et al. Randomized comparison of allogeneic versus autologous mesenchymal stem cells for nonischemic dilated cardiomyopathy: POSEIDON-DCM Trial. J Am Coll Cardiol. 2017;69(5):526–537. doi: 10.1016/j.jacc.2016.11.009Mu Y, Cao G, Zeng Q, Li Y. Transplantation of induced bone marrow mesenchymal stem cells improves the cardiac function of rabbits with dilated cardiomyopathy via upregulation of vascular endothelial growth factor and its receptors. Exp Biol Med (Maywood). 2011;236(9):1100–1107. doi: 10.1258/ebm.2011.011066Yang S, Piao J, Jin L, Zhou Y. Does pretreatment of bone marrow mesenchymal stem cells with 5-azacytidine or double intravenous infusion improve their therapeutic potential for dilated cardiomyopathy? Med Sci Monit Basic Res. 2013;19:20–31. doi: 10.12659/msmbr.883737Nagaya N, Kangawa K, Itoh T, et al. Transplantation of mesenchymal stem cells improves cardiac function in a rat model of dilated cardiomyopathy. Circulation. 2005;112(8):1128–1135. doi: 10.1161/CIRCULATIONAHA.104.500447Gong X, Wang P, Wu Q, et al. Human umbilical cord blood derived mesenchymal stem cells improve cardiac function in cTnT(R141W) transgenic mouse of dilated cardiomyopathy. Eur J Cell Biol. 2016;95(1):57–67. doi: 10.1016/j.ejcb.2015.11.003Mao C, Hou X, Wang B, et al. Intramuscular injection of human umbilical cord-derived mesenchymal stem cells improves cardiac function in dilated cardiomyopathy rats. Stem Cell Res Ther. 2017;8(1):18. doi: 10.1186/s13287-017-0472-y EDN: VFJVTBLin YC, Leu S, Sun CK, et al. Early combined treatment with sildenafil and adipose-derived mesenchymal stem cells preserves heart function in rat dilated cardiomyopathy. J Transl Med. 2010;8:88. doi: 10.1186/1479-5876-8-88 EDN: YBNCIVMori D, Miyagawa S, Kido T, et al. Adipose-derived mesenchymal stem cells preserve cardiac function via ANT-1 in dilated cardiomyopathy hamster model. Regen Ther. 2021;18:182–190. doi: 10.1016/j.reth.2021.06.006 EDN: LGEABZKrupnova AD, Tsomartova DA, Chereshneva EV, et al. Mitochondrial donation as a mechanism of participation of mesenchymal stromal cells in regenerative processes. Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology. 2024;18(4):275–284. doi: 10.1134/S1990747824700272 EDN: OMTHDYAcquistapace A, Bru T, Lesault PF, et al. Human mesenchymal stem cells reprogram adult cardiomyocytes toward a progenitor-like state through partial cell fusion and mitochondria transfer. Stem Cells. 2011;29(5):812–824. doi: 10.1002/stem.632 EDN: OMSDTDAbushouk AI, Salem AMA, Saad A, et al. Mesenchymal stem cell therapy for doxorubicin-induced cardiomyopathy: potential mechanisms, governing factors, and implications of the heart stem cell debate. Front Pharmacol. 2019;10:635. doi: 10.3389/fphar.2019.00635 EDN: LBUGDIValle-Prieto A, Conget PA. Human mesenchymal stem cells efficiently manage oxidative stress. Stem Cells Dev. 2010;19(12):1885–1893. doi: 10.1089/scd.2010.0093Zaki SM, Algaleel WA, Imam RA, Abdelmoaty MM. Mesenchymal stem cells pretreated with platelet-rich plasma modulate doxorubicin-induced cardiotoxicity. Hum Exp Toxicol. 2019;38(7):857–874. doi: 10.1177/0960327119842613 EDN: CITCGQSun X, Shan A, Wei Z, Xu B. Intravenous mesenchymal stem cell-derived exosomes ameliorate myocardial inflammation in the dilated cardiomyopathy. Biochem Biophys Res Commun. 2018;503(4):2611–2618. doi: 10.1016/j.bbrc.2018.08.012Gong C, Chang L, Sun X, et al. Infusion of two-dose mesenchymal stem cells is more effective than a single dose in a dilated cardiomyopathy rat model by upregulating indoleamine 2,3-dioxygenase expression. Stem Cell Res Ther. 2022;13(1):409. doi: 10.1186/s13287-022-03101-w EDN: FUHPXQBernardo ME, Fibbe WE. Mesenchymal stromal cells: sensors and switchers of inflammation. Cell Stem Cell. 2013;13(4):392–402. doi: 10.1016/j.stem.2013.09.006 EDN: YAKGQHMartire A, Bedada FB, Uchida S, et al. Mesenchymal stem cells attenuate inflammatory processes in the heart and lung via inhibition of TNF signaling. Basic Res Cardiol. 2016;111(5):54. doi: 10.1007/s00395-016-0573-2 EDN: ZYHXMJCarmona MD, Cañadillas S, Romero M, et al. Intramyocardial bone marrow mononuclear cells versus bone marrow-derived and adipose mesenchymal cells in a rat model of dilated cardiomyopathy. Cytotherapy. 2017;19(8):947–961. doi: 10.1016/j.jcyt.2017.05.006Premer C, Blum A, Bellio MA, et al. Allogeneic mesenchymal stem cells restore endothelial function in heart failure by stimulating endothelial progenitor cells. EBioMedicine. 2015;2(5):467–475. doi: 10.1016/j.ebiom.2015.03.020 EDN: WOMKABPremer C, Wanschel A, Porras V, et al. Mesenchymal stem cell secretion of SDF-1α modulates endothelial function in dilated cardiomyopathy. Front Physiol. 2019;10:1182. doi: 10.3389/fphys.2019.01182Vasina EYu, Malakhova ZL, Anosov IA, et al. Assessment of endothelium-dependent vasodilation in the clinic: what endothelial factor are we studying? Arterial’naya gipertenziya. 2020;26(2):211–218. doi: 10.18705/1607-419X-2020-26-2-211-218 EDN: KTMYWNYu Q, Li Q, Na R, et al. Impact of repeated intravenous bone marrow mesenchymal stem cells infusion on myocardial collagen network remodeling in a rat model of doxorubicin-induced dilated cardiomyopathy. Mol Cell Biochem. 2014;387(1-2):279–285. doi: 10.1007/s11010-013-1894-1 EDN: OQZQRGYu Q, Fang W, Zhu N, et al. Beneficial effects of intramyocardial mesenchymal stem cells and VEGF165 plasmid injection in rats with furazolidone induced dilated cardiomyopathy. J Cell Mol Med. 2015;19(8):1868–1876. doi: 10.1111/jcmm.12558Zhang C, Zhou G, Chen Y, et al. Human umbilical cord mesenchymal stem cells alleviate interstitial fibrosis and cardiac dysfunction in a dilated cardiomyopathy rat model by inhibiting TNF-α and TGF-β1/ERK1/2 signaling pathways. Mol Med Rep. 2018;17(1):71–78. doi: 10.3892/mmr.2017.7882Zhang C, Zhou Y, Lai X, et al. Human umbilical cord mesenchymal stem cells alleviate myocardial endothelial-mesenchymal transition in a rat dilated cardiomyopathy model. Transplant Proc. 2019;51(3):936–941. doi: 10.1016/j.transproceed.2019.01.080Wang JA, Xie XJ, He H, et al. A prospective, randomized, controlled trial of autologous mesenchymal stem cells transplantation for dilated cardiomyopathy. Zhonghua Xin Xue Guan Bing Za Zhi. 2006;34(2):107–110. (In Chinese).Zeinaloo A, Zanjani KS, Bagheri MM, et al. Intracoronary administration of autologous mesenchymal stem cells in a critically ill patient with dilated cardiomyopathy. Pediatr Transplant. 2011;15(8):E183–E186. doi: 10.1111/j.1399-3046.2010.01366.xChin SP, Poey AC, Wong CY, et al. Intramyocardial and intracoronary autologous bone marrow-derived mesenchymal stromal cell treatment in chronic severe dilated cardiomyopathy. Cytotherapy. 2011;13(7):814–821. doi: 10.3109/14653249.2011.574118Xiao W, Guo S, Gao C, et al. A randomized comparative study on the efficacy of intracoronary infusion of autologous bone marrow mononuclear cells and mesenchymal stem cells in patients with dilated cardiomyopathy. Int Heart J. 2017;58(2):238–244. doi: 10.1536/ihj.16-328Rieger AC, Myerburg RJ, Florea V, et al. Genetic determinants of responsiveness to mesenchymal stem cell injections in non-ischemic dilated cardiomyopathy. EBioMedicine. 2019;48:377–385. doi: 10.1016/j.ebiom.2019.09.043Saltzman RG, Sundin A, Caceres LV, et al. Long term event-free survival following cell-based therapy in patients with cardiomyopathy: the HYPERION observational cohort. Stem Cells Transl Med. 2025;14(5):szaf010. doi: 10.1093/stcltm/szaf010 EDN: SUOGLMLatipbaeva MS, Askarov MB, Seysembekov TZ, Mazhanova АТ. To study the effectiveness of the administration of bone marrow mesenchymal stem cells in patients with dilated and ischemic cardiomyopathy. In: Collection of scientific papers of the III interuniversity conference on somatic diseases. Moscow: Foundation for the Promotion of Cardiology Development “Cardioprogress”; 2024. P. 9–10. EDN: STBVYQHuynh K. Stem cells: Allogenic mesenchymal stem cells for dilated cardiomyopathy. Nat Rev Cardiol. 2017;14(4):190–191. doi: 10.1038/nrcardio.2017.21Kanelidis AJ, Premer C, Lopez J, et al. Route of delivery modulates the efficacy of mesenchymal stem cell therapy for myocardial infarction: a meta-analysis of preclinical studies and clinical trials. Circ Res. 2017;120(7):1139–1150. doi: 10.1161/CIRCRESAHA.116.309819Sheu JJ, Chai HT, Sung PH, et al. Double overexpression of miR-19a and miR-20a in induced pluripotent stem cell-derived mesenchymal stem cells effectively preserves the left ventricular function in dilated cardiomyopathic rat. Stem Cell Res Ther. 2021;12(1):371. doi: 10.1186/s13287-021-02440-4 EDN: BSNSBHLin H, Ling Y, Pan J, Gong H. Therapeutic effects of erythropoietin expressed in mesenchymal stem cells for dilated cardiomyopathy in rat. Biochem Biophys Res Commun. 2019;517(4):575–580. doi: 10.1016/j.bbrc.2019.07.053Lee JY, Chung J, Byun Y, et al. Mesenchymal stem cell-derived small extracellular vesicles protect cardiomyocytes from doxorubicin-induced cardiomyopathy by upregulating survivin expression via the miR-199a-3p-Akt-Sp1/p53 signaling pathway. Int J Mol Sci. 2021;22(13):7102. doi: 10.3390/ijms22137102 EDN: PXGKJG