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2000
Volume 20, Issue 9
  • ISSN: 1574-888X
  • E-ISSN: 2212-3946

Abstract

Autoimmune diseases pose a significant challenge due to their complex pathogenesis and rising prevalence. Traditional therapies are often limited by systemic side effects, immunosuppression, and lack of long-term efficacy. Mesenchymal stem cells (MSCs) have demonstrated immunomodulatory properties, primarily through the secretion of extracellular vesicles (EVs), which are now recognized as potent mediators of immune regulation. MSC-derived EVs carry bioactive molecules such as microRNAs, proteins, and lipids that influence key immune pathways, making them a promising therapeutic avenue for autoimmune diseases. This review critically examines the immunomodulatory mechanisms of MSC-derived EVs, focusing on their role in regulating T cells, B cells, and macrophages, which are central to autoimmune pathology. We explore recent preclinical and clinical studies that highlight the ability of MSC-derived EVs to reduce inflammation, promote immune tolerance, and restore tissue homeostasis in autoimmune settings. Furthermore, we discuss the advantages of EV-based therapy over MSC-based therapies, including improved safety profiles, lower immunogenicity, and scalability for clinical application. By evaluating the current landscape of MSC-derived EV research, we identify key gaps and propose innovative strategies to optimize EV-based therapies for autoimmune diseases. These strategies include engineering EVs to enhance their specificity and therapeutic efficacy, as well as integrating them with biomaterials for targeted delivery. Our review aims to provide a forward-looking perspective on the potential of MSC-derived EVs as a novel therapeutic approach, moving beyond traditional cell-based therapies to offer more precise and personalized treatment options for autoimmune diseases.

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2025-12-27
2025-12-09

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References

  1. RosenblumM.D. RemediosK.A. AbbasA.K. Mechanisms of human autoimmunity.J. Clin. Invest.201512562228223310.1172/JCI78088 25893595
     [Google Scholar]
  2. WenJ. ZhangJ. ZhangH. Large-scale genome-wide association studies reveal the genetic causal etiology between air pollutants and autoimmune diseases.J. Transl. Med.202422139210.1186/s12967‑024‑04928‑y 38685026
     [Google Scholar]
  3. SmithD.A. GermolecD.R. “Introduction to immunology and autoimmunity,” (in eng).Environ. Health Perspect.107Suppl. 566166510.1289/ehp.99107s5661
     [Google Scholar]
  4. HaqueN. RamasamyT.S. KasimN.H.A. Mechanisms of mesenchymal stem cells for autoimmune disease treatment.Stem Cell Transplant Autoimmun Inflamm2019274410.1007/978‑3‑030‑23421‑8_2
     [Google Scholar]
  5. AngumF. KhanT. KalerJ. SiddiquiL. HussainA. The prevalence of autoimmune disorders in women: a narrative review.Cureus2020125e8094e410.7759/cureus.8094 32542149
     [Google Scholar]
  6. HussainM.S. ChaturvediV. The present condition of sickle cell disease: an overview of stem cell transplantation as a cure.Pharm Fronts202352e57e6310.1055/s‑0043‑1768918
     [Google Scholar]
  7. RadF. GhorbaniM. Mohammadi RoushandehA. Habibi RoudkenarM. Mesenchymal stem cell-based therapy for autoimmune diseases: emerging roles of extracellular vesicles.Mol. Biol. Rep.20194611533154910.1007/s11033‑019‑04588‑y 30623280
     [Google Scholar]
  8. BahlG. PathakY. HussainM.S. GuptaY. SaraswatN. Navigating Sheehan syndrome’s silent onset: A case report.J. Clin. Transl. Endocrinol. Case Rep.20243210016810.1016/j.jecr.2024.100168
     [Google Scholar]
  9. TyndallA. Successes and failures of stem cell transplantation in autoimmune diseases.Hematology (Am. Soc. Hematol. Educ. Program)20112011128028410.1182/asheducation‑2011.1.280 22160046
     [Google Scholar]
  10. BaharlooiH. AzimiM. SalehiZ. IzadM. Mesenchymal stem cell-derived exosomes: a promising therapeutic ace card to address autoimmune diseases.Int. J. Stem Cells2020131132310.15283/ijsc19108 31887849
     [Google Scholar]
  11. GuptaG. HussainM.S. ThapaR. Hope on the horizon: Wharton’s jelly mesenchymal stem cells in the fight against COVID-19.Regen. Med.202318967567810.2217/rme‑2023‑0077 37554111
     [Google Scholar]
  12. ZhuoY. LiW.S. LuW. TGF-β1 mediates hypoxia-preconditioned olfactory mucosa mesenchymal stem cells improved neural functional recovery in Parkinson’s disease models and patients.Mil. Med. Res.20241114810.1186/s40779‑024‑00550‑7 39034405
     [Google Scholar]
  13. Luque-CamposN Mesenchymal stem cells improve rheumatoid arthritis progression by controlling memory T cell response.Front Immunol Rev20191079810.3389/fimmu.2019.00798
     [Google Scholar]
  14. CiprianiP. CarubbiF. LiakouliV. Stem cells in autoimmune diseases: Implications for pathogenesis and future trends in therapy.Autoimmun. Rev.201312770971610.1016/j.autrev.2012.10.004 23183379
     [Google Scholar]
  15. TianS. ChenX. WuW. Nucleus pulposus cells regulate macrophages in degenerated intervertebral discs via the integrated stress response-mediated CCL2/7-CCR2 signaling pathway.Exp. Mol. Med.202456240842110.1038/s12276‑024‑01168‑4 38316963
     [Google Scholar]
  16. LanZ. TanF. HeJ. Curcumin-primed olfactory mucosa-derived mesenchymal stem cells mitigate cerebral ischemia/reperfusion injury-induced neuronal PANoptosis by modulating microglial polarization.Phytomedicine202412915563510.1016/j.phymed.2024.155635 38701541
     [Google Scholar]
  17. SeoY. KimH-S. HongI-S. Stem cell-derived extracellular vesicles as immunomodulatory therapeutics.Stem Cells International2019512615610.1155/2019/5126156
     [Google Scholar]
  18. Sadique HussainM Exosomal ncRNAs in liquid biopsies for lung cancer. Int J Clini Chem202456511998310.1016/j.cca.2024.119983
     [Google Scholar]
  19. CooperG.S. BynumM.L.K. SomersE.C. Recent insights in the epidemiology of autoimmune diseases: Improved prevalence estimates and understanding of clustering of diseases.J. Autoimmun.2009333-419720710.1016/j.jaut.2009.09.008 19819109
     [Google Scholar]
  20. YamamotoK. Introduction: autoimmunity special issue.Int. Immunol.201628415315410.1093/intimm/dxw010 27034456
     [Google Scholar]
  21. OkadaH. KuhnC. FeilletH. BachJ-F. The ‘hygiene hypothesis’ for autoimmune and allergic diseases: an update.Clin. Exp. Immunol.201016011910.1111/j.1365‑2249.2010.04139.x 20415844
     [Google Scholar]
  22. BolonB. Cellular and molecular mechanisms of autoimmune disease.Toxicol. Pathol.201240221622910.1177/0192623311428481 22105648
     [Google Scholar]
  23. YangS.H. GaoC. LiL. The molecular basis of immune regulation in autoimmunity.Clin. Sci.20181321436710.1042/CS20171154 29305419
     [Google Scholar]
  24. ChandrashekaraS. The treatment strategies of autoimmune disease may need a different approach from conventional protocol: A review.Indian J. Pharmacol.201244666567110.4103/0253‑7613.103235 23248391
     [Google Scholar]
  25. Blázquez-PruneraA. AlmeidaC. BarbosaM. Human bone marrow mesenchymal stem/stromal cells preserve their immunomodulatory and chemotactic properties when expanded in a human plasma derived xeno-free medium.Stem Cells Int.20172017110.1155/2017/2185351
     [Google Scholar]
  26. FrançoisM. Romieu-MourezR. LiM. GalipeauJ. Human MSC suppression correlates with cytokine induction of indoleamine 2,3-dioxygenase and bystander M2 macrophage differentiation.Mol. Ther.201220118719510.1038/mt.2011.189 21934657
     [Google Scholar]
  27. EngelaA.U. HoogduijnM.J. BoerK. Human adipose-tissue derived mesenchymal stem cells induce functional de-novo regulatory T cells with methylated FOXP3 gene DNA.Clin. Exp. Immunol.2013173234335410.1111/cei.12120 23607314
     [Google Scholar]
  28. GiesekeF. KruchenA. TzaribachevN. BentzienF. DominiciM. MüllerI. Proinflammatory stimuli induce galectin‐9 in human mesenchymal stromal cells to suppress T ‐cell proliferation.Eur. J. Immunol.201343102741274910.1002/eji.201343335 23817958
     [Google Scholar]
  29. HindenL. ShainerR. Almogi-HazanO. OrR. Ex vivo induced regulatory human/murine mesenchymal stem cells as immune modulators.Stem Cells20153372256226710.1002/stem.2026 25850816
     [Google Scholar]
  30. HuangF. ChenM. ChenW. Human gingiva-derived mesenchymal stem cells inhibit xeno-graft-versus-host disease via CD39–CD73–adenosine and IDO signals.Front. Immunol.201786810.3389/fimmu.2017.00068 28210258
     [Google Scholar]
  31. BaiL. LennonD.P. EatonV. Human bone marrow‐derived mesenchymal stem cells induce Th2‐polarized immune response and promote endogenous repair in animal models of multiple sclerosis.Glia200957111192120310.1002/glia.20841 19191336
     [Google Scholar]
  32. UccelliA. LaroniA. BrundinL. MESEMS study group Mesenchymal Stem cells for Multiple Sclerosis (MESEMS): a randomized, double blind, cross-over phase I/II clinical trial with autologous mesenchymal stem cells for the therapy of multiple sclerosis.Trials201920126310.1186/s13063‑019‑3346‑z 31072380
     [Google Scholar]
  33. HouZ. LiuY. MaoX.H. Transplantation of umbilical cord and bone marrow-derived mesenchymal stem cells in a patient with relapsing-remitting multiple sclerosis.Cell Adhes. Migr.20137540440710.4161/cam.26941 24192520
     [Google Scholar]
  34. YanL. JiangB. NiuY. Intrathecal delivery of human ESC-derived mesenchymal stem cell spheres promotes recovery of a primate multiple sclerosis model.Cell Death Discov.2018418910.1038/s41420‑018‑0091‑0 30131877
     [Google Scholar]
  35. ZafranskayaM. NizheharodavaD. YurkevichM. PGE2 contributes to in vitro MSC-mediated inhibition of non-specific and antigen-specific T cell proliferation in MS patients.Scand. J. Immunol.201378545546210.1111/sji.12102 23944654
     [Google Scholar]
  36. ZhangH. LiangJ. TangX. Sustained benefit from combined plasmapheresis and allogeneic mesenchymal stem cells transplantation therapy in systemic sclerosis.Arthritis Res. Ther.201719116510.1186/s13075‑017‑1373‑2 28724445
     [Google Scholar]
  37. ChangJ.W. HungS.P. WuH.H. Therapeutic effects of umbilical cord blood-derived mesenchymal stem cell transplantation in experimental lupus nephritis.Cell Transplant.201120224525810.3727/096368910X520056 20719085
     [Google Scholar]
  38. ChenJ Umbilical cord-derived mesenchymal stem cells suppress autophagy of T cells in patients with systemic lupus erythematosus via transfer of mitochondria Stem cells Int2016201610.1155/2016/4062789
     [Google Scholar]
  39. ChoiE.W. ShinI.S. ParkS.Y. Reversal of serologic, immunologic, and histologic dysfunction in mice with systemic lupus erythematosus by long‐term serial adipose tissue–derived mesenchymal stem cell transplantation.Arthritis Rheum.201264124325310.1002/art.33313 21904997
     [Google Scholar]
  40. LiX. WangD. LiangJ. ZhangH. SunL. Mesenchymal SCT ameliorates refractory cytopenia in patients with systemic lupus erythematosus.Bone Marrow Transplant.201348454455010.1038/bmt.2012.184 23064040
     [Google Scholar]
  41. ParkM.J. KwokS.K. LeeS.H. KimE.K. ParkS.H. ChoM.L. Adipose tissue-derived mesenchymal stem cells induce expansion of interleukin-10-producing regulatory B cells and ameliorate autoimmunity in a murine model of systemic lupus erythematosus.Cell Transplant.201524112367237710.3727/096368914X685645 25506685
     [Google Scholar]
  42. AlunnoA. MontanucciP. BistoniO. In vitro immunomodulatory effects of microencapsulated umbilical cord Wharton jelly-derived mesenchymal stem cells in primary Sjögren’s syndrome.Rheumatology201554116316810.1093/rheumatology/keu292 25065014
     [Google Scholar]
  43. HaiB. Shigemoto-KurodaT. ZhaoQ. LeeR.H. LiuF. Inhibitory effects of iPSC-MSCs and their extracellular vesicles on the onset of sialadenitis in a mouse model of Sjögren’s syndrome.Stem Cells Int.201820181209231510.1155/2018/209231529736173
     [Google Scholar]
  44. KhaliliS. LiuY. KorneteM. Mesenchymal stromal cells improve salivary function and reduce lymphocytic infiltrates in mice with Sjögren’s-like disease.PLoS One201276e3861510.1371/journal.pone.0038615 22685592
     [Google Scholar]
  45. LiuR. SuD. ZhouM. FengX. LiX. SunL. Umbilical cord mesenchymal stem cells inhibit the differentiation of circulating T follicular helper cells in patients with primary Sjögren’s syndrome through the secretion of indoleamine 2,3-dioxygenase.Rheumatology201554233234210.1093/rheumatology/keu316 25169988
     [Google Scholar]
  46. ForbesG.M. SturmM.J. LeongR.W. A phase 2 study of allogeneic mesenchymal stromal cells for luminal Crohn’s disease refractory to biologic therapy.Clin. Gastroenterol. Hepatol.2014121647110.1016/j.cgh.2013.06.021 23872668
     [Google Scholar]
  47. GonzálezM.A. Gonzalez-ReyE. RicoL. BüscherD. DelgadoM. Adipose-derived mesenchymal stem cells alleviate experimental colitis by inhibiting inflammatory and autoimmune responses.Gastroenterology2009136397898910.1053/j.gastro.2008.11.041 19135996
     [Google Scholar]
  48. ZhangJ. LvS. LiuX. SongB. ShiL. Umbilical cord mesenchymal stem cell treatment for Crohn’s disease: a randomized controlled clinical trial.Gut Liver2018121737810.5009/gnl17035 28873511
     [Google Scholar]
  49. SahS.K. AgrahariG. NguyenC.T. KimY.S. KangK.S. KimT.Y. Enhanced therapeutic effects of human mesenchymal stem cells transduced with superoxide dismutase 3 in a murine atopic dermatitis‐like skin inflammation model.Allergy201873122364237610.1111/all.13594 30144097
     [Google Scholar]
  50. VillatoroA.J. Hermida-PrietoM. FernándezV. Allogeneic adipose‐derived mesenchymal stem cell therapy in dogs with refractory atopic dermatitis: clinical efficacy and safety.Vet. Rec.201818321654410.1136/vr.104867 30158120
     [Google Scholar]
  51. WangM. YuanQ. XieL. Mesenchymal Stem Cell-Based Immunomodulation: Properties and Clinical Application.Stem Cells Int.2018201811210.1155/2018/3057624 30013600
     [Google Scholar]
  52. YiT. SongS.U. Immunomodulatory properties of mesenchymal stem cells and their therapeutic applications.Arch. Pharm. Res.201235221322110.1007/s12272‑012‑0202‑z 22370776
     [Google Scholar]
  53. LiP. OuQ. ShiS. ShaoC. Immunomodulatory properties of mesenchymal stem cells/dental stem cells and their therapeutic applications.Cell. Mol. Immunol.202320655856910.1038/s41423‑023‑00998‑y 36973490
     [Google Scholar]
  54. GaoF. ChiuS.M. MotanD A L. Mesenchymal stem cells and immunomodulation: current status and future prospects.Cell Death Dis.201671e2062210.1038/cddis.2015.327 26794657
     [Google Scholar]
  55. PlockJ.A. SchniderJ.T. SolariM.G. ZhengX.X. GorantlaV.S. Perspectives on the use of mesenchymal stem cells in vascularized composite allotransplantation.Front. Immunol.2013417510.3389/fimmu.2013.00175 23888159
     [Google Scholar]
  56. HaqueN. KasimN.H.A. RahmanM.T. Optimization of pre-transplantation conditions to enhance the efficacy of mesenchymal stem cells.Int. J. Biol. Sci.201511332433410.7150/ijbs.10567 25678851
     [Google Scholar]
  57. GeblerA. ZabelO. SeligerB. The immunomodulatory capacity of mesenchymal stem cells.Trends Mol. Med.201218212813410.1016/j.molmed.2011.10.004 22118960
     [Google Scholar]
  58. DuanW.W. YangL.T. LiuJ. A TGF‐β signaling‐related lncRNA signature for prediction of glioma prognosis, immune microenvironment, and immunotherapy response.CNS Neurosci. Ther.2024304e1448910.1111/cns.14489 37850692
     [Google Scholar]
  59. GangulyD. HaakS. SisirakV. ReizisB. The role of dendritic cells in autoimmunity.Nat. Rev. Immunol.201313856657710.1038/nri3477 23827956
     [Google Scholar]
  60. SozzaniS. Del PreteA. BosisioD. Dendritic cell recruitment and activation in autoimmunity.J. Autoimmun.20178512614010.1016/j.jaut.2017.07.012 28774715
     [Google Scholar]
  61. ShlomchikM.J. Activating systemic autoimmunity: B’s, T’s, and tolls.Curr. Opin. Immunol.200921662663310.1016/j.coi.2009.08.005 19800208
     [Google Scholar]
  62. ZaborowskiM.P. BalajL. BreakefieldX.O. LaiC.P. Extracellular vesicles: composition, biological relevance, and methods of study.Bioscience201565878379710.1093/biosci/biv084 26955082
     [Google Scholar]
  63. Yáñez-MóM. SiljanderP.R.M. AndreuZ. Biological properties of extracellular vesicles and their physiological functions.J. Extracell. Vesicles2015412706610.3402/jev.v4.27066 25979354
     [Google Scholar]
  64. ChengY. CaoX. QinL. Mesenchymal Stem Cell-Derived Extracellular Vesicles: A Novel Cell-Free Therapy for Sepsis.Front. Immunol.20201164710.3389/fimmu.2020.00647 32373121
     [Google Scholar]
  65. CorbeilD. LoricoA. Exosomes, microvesicles, and their friends in solid tumors.In: Exosomes.Elsevier2020398010.1016/B978‑0‑12‑816053‑4.00003‑1
     [Google Scholar]
  66. JasoriaY. Role of Exosomes in Multiple Sclerosis.In: Exosomes Based Drug Delivery Strategies for Brain Disorders.Springer202410312110.1007/978‑981‑99‑8373‑5_4
     [Google Scholar]
  67. YuG. DingJ. YangN. Evaluating the pro-survival potential of apoptotic bodies derived from 2D- and 3D- cultured adipose stem cells in ischaemic flaps.J. Nanobiotechnology202422133310.1186/s12951‑024‑02533‑1 38877492
     [Google Scholar]
  68. EdgarJ.R. EdenE.R. FutterC.E. Hrs- and CD63-dependent competing mechanisms make different sized endosomal intraluminal vesicles.Traffic201415219721110.1111/tra.12139 24279430
     [Google Scholar]
  69. WaniT.U. Exosomes Harnessed as Nanocarriers for Cancer Therapy-Current Status and Potential for Future Clinical Applications.Curr. Mol. Med.202010.2174/1566524020666200915111618 32933459
     [Google Scholar]
  70. RaposoG. StoorvogelW. Extracellular vesicles: Exosomes, microvesicles, and friends.J. Cell Biol.2013200437338310.1083/jcb.201211138 23420871
     [Google Scholar]
  71. KalraH. DrummenG. MathivananS. Focus on extracellular vesicles: introducing the next small big thing.Int. J. Mol. Sci.201617217010.3390/ijms17020170 26861301
     [Google Scholar]
  72. WhittakerT.E. NagelkerkeA. NeleV. KauscherU. StevensM.M. Experimental artefacts can lead to misattribution of bioactivity from soluble mesenchymal stem cell paracrine factors to extracellular vesicles.J. Extracell. Vesicles202091180767410.1080/20013078.2020.1807674 32944192
     [Google Scholar]
  73. WitwerK.W. Van BalkomB.W.M. BrunoS. Defining mesenchymal stromal cell (MSC)‐derived small extracellular vesicles for therapeutic applications.J. Extracell. Vesicles201981160920610.1080/20013078.2019.1609206 31069028
     [Google Scholar]
  74. ZhaoM. KangM. WangJ. Stem Cell‐Derived Nanovesicles Embedded in Dual‐Layered Hydrogel for Programmed ROS Regulation and Comprehensive Tissue Regeneration in Burn Wound Healing.Adv. Mater.20243632240136910.1002/adma.202401369 38822749
     [Google Scholar]
  75. ZhaoAG ShahK CromerB SumerH Mesenchymal Stem Cell-Derived Extracellular Vesicles and Their Therapeutic Potential Stem cells Int202018825771.10.1155/2020/882577132908543
     [Google Scholar]
  76. ColomboM. RaposoG. ThéryC. Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles.Annu. Rev. Cell Dev. Biol.201430125528910.1146/annurev‑cellbio‑101512‑122326 25288114
     [Google Scholar]
  77. GouldS.J. RaposoG. As we wait: coping with an imperfect nomenclature for extracellular vesicles.J. Extracell. Vesicles2013212038910.3402/jev.v2i0.20389 24009890
     [Google Scholar]
  78. StahlP.D. RaposoG. Extracellular vesicles: exosomes and microvesicles, integrators of homeostasis.Physiology201934316917710.1152/physiol.00045.2018 30968753
     [Google Scholar]
  79. JohnstoneR.M. AdamM. HammondJ.R. OrrL. TurbideC. Vesicle formation during reticulocyte maturation. Association of plasma membrane activities with released vesicles (exosomes).J. Biol. Chem.1987262199412942010.1016/S0021‑9258(18)48095‑7 3597417
     [Google Scholar]
  80. BarryF.P. MurphyJ.M. Mesenchymal stem cells: clinical applications and biological characterization.Int. J. Biochem. Cell Biol.200436456858410.1016/j.biocel.2003.11.001 15010324
     [Google Scholar]
  81. KahminiF.R. ShahgaldiS. Therapeutic potential of mesenchymal stem cell-derived extracellular vesicles as novel cell-free therapy for treatment of autoimmune disorders.Exp. Mol. Pathol.202111810456610.1016/j.yexmp.2020.104566 33160961
     [Google Scholar]
  82. BiancoP. “Mesenchymal” stem cells.Annu. Rev. Cell Dev. Biol.201430167770410.1146/annurev‑cellbio‑100913‑013132 25150008
     [Google Scholar]
  83. LinaresR. TanS. GounouC. ArraudN. BrissonA.R. High‐speed centrifugation induces aggregation of extracellular vesicles.J. Extracell. Vesicles2015412950910.3402/jev.v4.29509 26700615
     [Google Scholar]
  84. WuM. OuyangY. WangZ. Isolation of exosomes from whole blood by integrating acoustics and microfluidics.Proc. Natl. Acad. Sci. USA201711440105841058910.1073/pnas.1709210114 28923936
     [Google Scholar]
  85. DoyleL. WangM. Overview of extracellular vesicles, their origin, composition, purpose, and methods for exosome isolation and analysis.Cells20198772710.3390/cells8070727 31311206
     [Google Scholar]
  86. LudwigA.K. De MiroschedjiK. DoeppnerT.R. Precipitation with polyethylene glycol followed by washing and pelleting by ultracentrifugation enriches extracellular vesicles from tissue culture supernatants in small and large scales.J. Extracell. Vesicles201871152810910.1080/20013078.2018.1528109 30357008
     [Google Scholar]
  87. YuL-L. ZhuJ. LiuJ. A comparison of traditional and novel methods for the separation of exosomes from human samples.BioMed Res. Int.20181363456310.1155/2018/3634563
     [Google Scholar]
  88. LyuZ. XinM. OystonD.R. Cause and consequence of heterogeneity in human mesenchymal stem cells: Challenges in clinical application.Pathol. Res. Pract.202426015535410.1016/j.prp.2024.155354 38870711
     [Google Scholar]
  89. BöingA.N. van der PolE. GrootemaatA.E. CoumansF.A.W. SturkA. NieuwlandR. Single‐step isolation of extracellular vesicles by size‐exclusion chromatography.J. Extracell. Vesicles2014312343010.3402/jev.v3.23430 25279113
     [Google Scholar]
  90. Del PiccoloN. PlaconeJ. HeL. AgudeloS.C. HristovaK. Production of plasma membrane vesicles with chloride salts and their utility as a cell membrane mimetic for biophysical characterization of membrane protein interactions.Anal. Chem.201284208650865510.1021/ac301776j 22985263
     [Google Scholar]
  91. SamahS RamasamyK LimS M NeohC F J r practice c. Probiotics for the management of type 2 diabetes mellitus: A systematic review and meta-analysis.Diab res clinic pract201611817282
     [Google Scholar]
  92. MaoF Exosomes derived from human umbilical cord mesenchymal stem cells relieve inflammatory bowel disease in mice.BioMed Res Int2017201710.1155/2017/5356760
     [Google Scholar]
  93. GomzikovaM.O. RizvanovA.A. Current trends in regenerative medicine: from cell to cell-free therapy.Bionanoscience20177124024510.1007/s12668‑016‑0348‑0
     [Google Scholar]
  94. GomzikovaM.O. AimaletdinovA.M. BondarO.V. Immunosuppressive properties of cytochalasin B-induced membrane vesicles of mesenchymal stem cells: comparing with extracellular vesicles derived from mesenchymal stem cells.Sci. Rep.20201011074010.1038/s41598‑020‑67563‑9 32612100
     [Google Scholar]
  95. XuL. LinM. LiY. LiS. ChenS. WeiC. Preparation of plasma membrane vesicles from bone marrow mesenchymal stem cells for potential cytoplasm replacement therapy.J. Vis. Exp.2017123e5574110.3791/55741‑v 28570530
     [Google Scholar]
  96. RobbK.P. FitzgeraldJ.C. BarryF. ViswanathanS. Mesenchymal stromal cell therapy: progress in manufacturing and assessments of potency.Cytotherapy201921328930610.1016/j.jcyt.2018.10.014 30528726
     [Google Scholar]
  97. MendtM. KamerkarS. SugimotoH. Generation and testing of clinical-grade exosomes for pancreatic cancer.JCI Insight201838e9926310.1172/jci.insight.99263 29669940
     [Google Scholar]
  98. BrakhageA.A. ZimmermannA.K. RivieccioF. VisserC. BlangoM.G. Host-derived extracellular vesicles for antimicrobial defense.MicroLife20212uqab00310.1093/femsml/uqab003 37223251
     [Google Scholar]
  99. LaiP. WengJ. GuoL. ChenX. DuX. Novel insights into MSC-EVs therapy for immune diseases.Biomark. Res.201971610.1186/s40364‑019‑0156‑0 30923617
     [Google Scholar]
  100. LaiR.C. ArslanF. LeeM.M. Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury.Stem Cell Res.20104321422210.1016/j.scr.2009.12.003 20138817
     [Google Scholar]
  101. JafariniaM. AlsahebfosoulF. SalehiH. EskandariN. Ganjalikhani-HakemiM. Mesenchymal stem cell-derived extracellular vesicles: a novel cell-free therapy.Immunol. Invest.202049775878010.1080/08820139.2020.1712416 32009478
     [Google Scholar]
  102. Al NaemM. BourebabaL. KucharczykK. RöckenM. MaryczK. Therapeutic mesenchymal stromal stem cells: Isolation, characterization and role in equine regenerative medicine and metabolic disorders.Stem Cell Rev. Rep.202016230132210.1007/s12015‑019‑09932‑0 31797146
     [Google Scholar]
  103. KangD. OhS. AhnS.M. LeeB.H. MoonM.H. Proteomic analysis of exosomes from human neural stem cells by flow field-flow fractionation and nanoflow liquid chromatography-tandem mass spectrometry.J. Proteome Res.2008783475348010.1021/pr800225z 18570454
     [Google Scholar]
  104. ZhengG. HuangR. QiuG. Mesenchymal stromal cell-derived extracellular vesicles: regenerative and immunomodulatory effects and potential applications in sepsis.Cell Tissue Res.2018374111510.1007/s00441‑018‑2871‑5 29955951
     [Google Scholar]
  105. LaiRC Proteolytic potential of the MSC exosome proteome: implications for an exosome-mediated delivery of therapeutic proteasome Int J Prot20122012
     [Google Scholar]
  106. BurrelloJ. MonticoneS. GaiC. GomezY. KholiaS. CamussiG. Stem cell-derived extracellular vesicles and immune-modulation.Front. Cell Dev. Biol.201648310.3389/fcell.2016.00083 27597941
     [Google Scholar]
  107. BebelmanM.P. SmitM.J. PegtelD.M. BaglioS.R. Biogenesis and function of extracellular vesicles in cancer.Pharmacol. Ther.201818811110.1016/j.pharmthera.2018.02.013 29476772
     [Google Scholar]
  108. ChandraS. VimalD. SharmaD. RaiV. GuptaS.C. ChowdhuriD.K. Role of miRNAs in development and disease: Lessons learnt from small organisms.Life Sci.201718581410.1016/j.lfs.2017.07.017 28728902
     [Google Scholar]
  109. ZhouY. LiQ. PanR. Regulatory roles of three miRNAs on allergen mRNA expression in Tyrophagus putrescentiae.Allergy202277246948210.1111/all.15111 34570913
     [Google Scholar]
  110. FonsatoV. CollinoF. HerreraM.B. Human liver stem cell-derived microvesicles inhibit hepatoma growth in SCID mice by delivering antitumor microRNAs.Stem Cells20123091985199810.1002/stem.1161 22736596
     [Google Scholar]
  111. OnoM. KosakaN. TominagaN. Exosomes from bone marrow mesenchymal stem cells contain a microRNA that promotes dormancy in metastatic breast cancer cells.Sci. Signal.20147332ra63ra310.1126/scisignal.2005231 24985346
     [Google Scholar]
  112. LeeJ.K. ParkS.R. JungB.K. Exosomes derived from mesenchymal stem cells suppress angiogenesis by down-regulating VEGF expression in breast cancer cells.PLoS One2013812e8425610.1371/journal.pone.0084256 24391924
     [Google Scholar]
  113. XinH. LiY. BullerB. Exosome-mediated transfer of miR-133b from multipotent mesenchymal stromal cells to neural cells contributes to neurite outgrowth.Stem Cells20123071556156410.1002/stem.1129 22605481
     [Google Scholar]
  114. WangJ. XiaJ. HuangR. Mesenchymal stem cell-derived extracellular vesicles alter disease outcomes via endorsement of macrophage polarization.Stem Cell Res. Ther.202011142410.1186/s13287‑020‑01937‑8 32993783
     [Google Scholar]
  115. BrunoS. DeregibusM.C. CamussiG. The secretome of mesenchymal stromal cells: Role of extracellular vesicles in immunomodulation.Immunol. Lett.2015168215415810.1016/j.imlet.2015.06.007 26086886
     [Google Scholar]
  116. LiuX. WeiQ. LuL. Immunomodulatory potential of mesenchymal stem cell-derived extracellular vesicles: Targeting immune cells.Front. Immunol.202314109468510.3389/fimmu.2023.1094685 36860847
     [Google Scholar]
  117. Franco da CunhaF. Andrade-OliveiraV. Candido de AlmeidaD. Extracellular Vesicles isolated from Mesenchymal Stromal Cells Modulate CD4+ T Lymphocytes Toward a Regulatory Profile.Cells202094105910.3390/cells9041059 32340348
     [Google Scholar]
  118. ChuH. DuC. YangY. MC-LR Aggravates Liver Lipid Metabolism Disorders in Obese Mice Fed a High-Fat Diet via PI3K/AKT/mTOR/SREBP1 Signaling Pathway.Toxins2022141283310.3390/toxins14120833 36548730
     [Google Scholar]
  119. XuA NF-κB pathway activation during endothelial-to-mesenchymal transition in a rat model of doxorubicin-induced cardiotoxicity BioPharm.202013011052510.1016/j.biopha.2020.110525
     [Google Scholar]
  120. GrangeC. TapparoM. BrunoS. Biodistribution of mesenchymal stem cell-derived extracellular vesicles in a model of acute kidney injury monitored by optical imaging.Int. J. Mol. Med.20143351055106310.3892/ijmm.2014.1663 24573178
     [Google Scholar]
  121. JangS.C. KimS.R. YoonY.J. In vivo kinetic biodistribution of nano-sized outer membrane vesicles derived from bacteria.Small201511445646110.1002/smll.201401803 25196673
     [Google Scholar]
  122. LaiC.P. MardiniO. EricssonM. Dynamic biodistribution of extracellular vesicles in vivo using a multimodal imaging reporter.ACS Nano20148148349410.1021/nn404945r 24383518
     [Google Scholar]
  123. WiklanderO.P.B. NordinJ.Z. O’LoughlinA. Extracellular vesicle in vivo biodistribution is determined by cell source, route of administration and targeting.J. Extracell. Vesicles2015412631610.3402/jev.v4.26316 25899407
     [Google Scholar]
  124. TamuraR. UemotoS. TabataY. Immunosuppressive effect of mesenchymal stem cell-derived exosomes on a concanavalin A-induced liver injury model.Inflamm. Regen.20163612610.1186/s41232‑016‑0030‑5 29259699
     [Google Scholar]
  125. CosenzaS. ToupetK. MaumusM. Mesenchymal stem cells-derived exosomes are more immunosuppressive than microparticles in inflammatory arthritis.Theranostics2018851399141010.7150/thno.21072 29507629
     [Google Scholar]
  126. MengQ. QiuB. Exosomal MicroRNA-320a Derived From Mesenchymal Stem Cells Regulates Rheumatoid Arthritis Fibroblast-Like Synoviocyte Activation by Suppressing CXCL9 Expression.Front. Physiol.20201144144110.3389/fphys.2020.00441 32528301
     [Google Scholar]
  127. LiZ. LiuF. HeX. YangX. ShanF. FengJ. Exosomes derived from mesenchymal stem cells attenuate inflammation and demyelination of the central nervous system in EAE rats by regulating the polarization of microglia.Int. Immunopharmacol.20196726828010.1016/j.intimp.2018.12.001 30572251
     [Google Scholar]
  128. JafariniaM. AlsahebfosoulF. SalehiH. Therapeutic effects of extracellular vesicles from human adipose‐derived mesenchymal stem cells on chronic experimental autoimmune encephalomyelitis.J. Cell. Physiol.2020235118779879010.1002/jcp.29721 32329062
     [Google Scholar]
  129. Laso-GarcíaF. Ramos-CejudoJ. Carrillo-SalinasF.J. Therapeutic potential of extracellular vesicles derived from human mesenchymal stem cells in a model of progressive multiple sclerosis.PLoS One2018139e020259010.1371/journal.pone.0202590 30231069
     [Google Scholar]
  130. ZhuZ. GuY. ZengC. Olanzapine-induced lipid disturbances: A potential mechanism through the gut microbiota-brain axis.Front. Pharmacol.20221389792610.3389/fphar.2022.897926 35991866
     [Google Scholar]
  131. Shigemoto-KurodaT. OhJ.Y. KimD. MSC-derived Extracellular Vesicles Attenuate Immune Responses in Two Autoimmune Murine Models: Type 1 Diabetes and Uveoretinitis.Stem Cell Reports2017851214122510.1016/j.stemcr.2017.04.008 28494937
     [Google Scholar]
  132. BaiL Effects of Mesenchymal Stem Cell-Derived Exosomes on Experimental Autoimmune Uveitis Sci Rep.201710.1038/s41598‑017‑04559‑y28659587
     [Google Scholar]
  133. YangJ. LiuX.X. FanH. Extracellular vesicles derived from bone marrow mesenchymal stem cells protect against experimental colitis via attenuating colon inflammation, oxidative stress and apoptosis.PLoS One20151010e014055110.1371/journal.pone.0140551 26469068
     [Google Scholar]
  134. WuY. Exosomes derived from human umbilical cord mesenchymal stem cells alleviate inflammatory bowel disease in mice through ubiquitination.Am. J. Transl. Res.201810720262036 30093940
     [Google Scholar]
  135. NojehdehiS. SoudiS. HesampourA. RasouliS. SoleimaniM. HashemiS.M. Immunomodulatory effects of mesenchymal stem cell–derived exosomes on experimental type‐1 autoimmune diabetes.J. Cell. Biochem.2018119119433944310.1002/jcb.27260 30074271
     [Google Scholar]
  136. BahlG. UpadhyayD.K. VarmaM. SinghR. DasS. HussainS. Persistent chronic calcific pancreatitis with intraductal calculi associated with secondary diabetes mellitus type 3 and diabetic ketoacidosis – A case report.Endocr. Regul.202458110110410.2478/enr‑2024‑0011 38656253
     [Google Scholar]
  137. SabryD. MarzoukS. ZakariaR. IbrahimH.A. SamirM. The effect of exosomes derived from mesenchymal stem cells in the treatment of induced type 1 diabetes mellitus in rats.Biotechnol. Lett.20204281597161010.1007/s10529‑020‑02908‑y 32430801
     [Google Scholar]
  138. ZhouY. Dermatophagoides pteronyssinus allergen Der p 22: Cloning, expression, IgE-binding in asthmatic children, and immunogenicity.Pediatr. Allergy Immunol.2022338e1383510.1111/pai.13835
     [Google Scholar]
  139. WangL. GuZ. ZhaoX. Extracellular vesicles released from human umbilical cord-derived mesenchymal stromal cells prevent life-threatening acute graft-versus-host disease in a mouse model of allogeneic hematopoietic stem cell transplantation.Stem Cells Dev.201625241874188310.1089/scd.2016.0107 27649744
     [Google Scholar]
/content/journals/cscr/10.2174/011574888X341781241216044130
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Immunomodulatory Roles of Mesenchymal Stem Cell-derived Extracellular Vesicles: A Promising Therapeutic Approach for Autoimmune Diseases
Curr Stem Cell Res Ther 20, 949 (2025); https://doi.org/10.2174/011574888X341781241216044130
/content/journals/cscr/10.2174/011574888X341781241216044130
/content/journals/cscr/10.2174/011574888X341781241216044130
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  • Article Type:     Review Article
Keyword(s): Autoimmunity; biomaterials; immunotherapy; inflammation; tolerance; wound healing

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