Skip to main content

Advertisement

SpringerLink
Log in

Progress in research on mesenchymal stem cells and their extracellular vesicles for treating fibrosis in systemic sclerosis

  • Review
  • Published:
Clinical and Experimental Medicine Aims and scope Submit manuscript

Abstract

Systemic sclerosis (SSc) refers to an autoimmune disease characterized by immune dysfunction, vascular endothelial damage, and multi-organ fibrosis. Thus far, this disease is incurable, and its high mortality rate is significantly correlated with fibrotic events. Fibrosis has been confirmed as a difficult clinical treatment area that should be urgently treated in clinical medicine. Mesenchymal stem cells (MSCs) exhibit immunomodulatory, pro-angiogenic, and anti-fibrotic functions. MSCs-derived extracellular vesicles (EVs) have aroused rising interest as a cellular component that retains the functions of MSCs while circumventing the possible adverse effects of MSCs. Moreover, EVs have great potential in treating SSc. In this study, the current research progress on MSCs and their EVs for treating fibrosis in SSc was reviewed, with an aim to provide some reference for future MSCs and their EVs in treating SSc.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Data availability

All data are available from the corresponding author.

Abbreviations

SSc:

Systemic sclerosis

MSCs:

Mesenchymal stem cells

EVs:

Extracellular vesicles

BMSCs:

Bone Marrow-derived stem cells

AMSCs:

Adipose-derived mesenchymal stem cells

TSG-6:

Tumor necrosis factor-stimulated gene 6

TSG101:

Tumor susceptibility gene 101

HSP:

Heat shock protein

BLM:

Bleomycin

WT:

Wild type

HGF:

Hepatocyte growth factor

LMWH:

Low molecular heparin

HOCl:

Hypochlorous acid

AOPPs:

Advanced oxidation protein products

Tsk:

Tight-skin

GVHD:

Chronic graft versus host disease

MRSS:

Modified rodnan skin scores

HAQ-DI:

Health assessment questionnaire disease activity index

PE:

Plasma exchange

GMP:

Good manufacturing practices

References

  1. Denton CP, Khanna D. Systemic sclerosis. Lancet (London, England). 2017;390(10103):1685–99.

    PubMed  Google Scholar 

  2. Jerjen R, Nikpour M, Krieg T, et al. Systemic sclerosis in adults. Part I: clinical features and pathogenesis. J Am Acad Dermatol. 2022;87(5):937–54.

    PubMed  Google Scholar 

  3. Bairkdar M, Rossides M, Westerlind H, et al. Incidence and prevalence of systemic sclerosis globally: a comprehensive systematic review and meta-analysis. Rheumatology (Oxford). 2021;60(7):3121–33.

    PubMed  Google Scholar 

  4. Elhai M, Meune C, Avouac J, et al. Trends in mortality in patients with systemic sclerosis over 40 years: a systematic review and meta-analysis of cohort studies. Rheumatology (Oxford). 2012;51(6):1017–26.

    PubMed  Google Scholar 

  5. Ramos-Casals M, Fonollosa-Pla V, Brito-Zerón P, et al. Targeted therapy for systemic sclerosis: how close are we? Nat Rev Rheumatol. 2010;6(5):269–78.

    CAS  PubMed  Google Scholar 

  6. Martin-Lopez M, Carreira PE. Antifibrotics in systemic sclerosis. Best Pract Res Clin Rheumatol. 2021;35(3):101671.

    PubMed  Google Scholar 

  7. Varrica C, Dias HS, Reis C, et al. Targeted delivery in scleroderma fibrosis. Autoimmun Rev. 2021;20(2):102730.

    CAS  PubMed  Google Scholar 

  8. Li A, Guo F, Pan Q, et al. Mesenchymal stem cell therapy: hope for patients with systemic lupus erythematosus. Front Immunol. 2021;12:728190.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Voswinkel J, Francois S, Simon JM, et al. Use of mesenchymal stem cells (MSC) in chronic inflammatory fistulizing and fibrotic diseases: a comprehensive review. Clin Rev Allergy Immunol. 2013;45(2):180–92.

    PubMed  Google Scholar 

  10. Casiraghi F, Remuzzi G, Abbate M, et al. Multipotent mesenchymal stromal cell therapy and risk of malignancies. Stem Cell Rev Rep. 2013;9(1):65–79.

    CAS  PubMed  Google Scholar 

  11. Rani S, Ryan AE, Griffin MD, et al. Mesenchymal stem cell-derived extracellular vesicles: toward cell-free therapeutic applications. Mol Ther. 2015;23(5):812–23.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Lv FJ, Tuan RS, Cheung KM, et al. Concise review: the surface markers and identity of human mesenchymal stem cells. Stem Cells. 2014;32(6):1408–19.

    CAS  PubMed  Google Scholar 

  13. Galipeau J, Sensébé L. Mesenchymal stromal cells: clinical challenges and therapeutic opportunities. Cell Stem Cell. 2018;22(6):824–33.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Ménard C, Tarte K. Immunoregulatory properties of clinical grade mesenchymal stromal cells: evidence, uncertainties, and clinical application. Stem Cell Res Ther. 2013;4(3):64.

    PubMed  PubMed Central  Google Scholar 

  15. Friedenstein AJ, Gorskaja JF, Kulagina NN. Fibroblast precursors in normal and irradiated mouse hematopoietic organs. Exp Hematol. 1976;4(5):267–74.

    CAS  PubMed  Google Scholar 

  16. Zhou SL, Zheng C, Su JQ, et al. Isolation and identification of human umbilical cord and placenta-derived stem cells and their component analysis. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2015;23(6):1684–91.

    CAS  PubMed  Google Scholar 

  17. Mebarki M, Abadie C, Larghero J, et al. Human umbilical cord-derived mesenchymal stem/stromal cells: a promising candidate for the development of advanced therapy medicinal products. Stem Cell Res Ther. 2021;12(1):152.

    PubMed  PubMed Central  Google Scholar 

  18. Puissant B, Barreau C, Bourin P, et al. Immunomodulatory effect of human adipose tissue-derived adult stem cells: comparison with bone marrow mesenchymal stem cells. Br J Haematol. 2005;129(1):118–29.

    PubMed  Google Scholar 

  19. Ménard C, Dulong J, Roulois D, et al. Integrated transcriptomic, phenotypic, and functional study reveals tissue-specific immune properties of mesenchymal stromal cells. Stem Cells. 2020;38(1):146–59.

    PubMed  Google Scholar 

  20. Loisel S, Dulong J, MéNARD C, et al. Brief report: proteasomal indoleamine 2,3-dioxygenase degradation reduces the immunosuppressive potential of clinical grade-mesenchymal stromal cells undergoing replicative senescence. Stem Cells. 2017;35(5):1431–6.

    CAS  PubMed  Google Scholar 

  21. Shi Y, Wang Y, Li Q, et al. Immunoregulatory mechanisms of mesenchymal stem and stromal cells in inflammatory diseases. Nat Rev Nephrol. 2018;14(8):493–507.

    CAS  PubMed  Google Scholar 

  22. Maumus M, Guérit D, Toupet K, et al. Mesenchymal stem cell-based therapies in regenerative medicine: applications in rheumatology. Stem Cell Res Ther. 2011;2(2):14.

    PubMed  PubMed Central  Google Scholar 

  23. Farge D, Loisel S, Lansiaux P, et al. Mesenchymal stromal cells for systemic sclerosis treatment. Autoimmun Rev. 2021;20(3):102755.

    CAS  PubMed  Google Scholar 

  24. Chen W, Xia ZK, Zhang MH, et al. Adipose tissue-derived stem cells ameliorates dermal fibrosis in a mouse model of scleroderma. Asian Pac J Trop Med. 2017;10(1):52–6.

    CAS  PubMed  Google Scholar 

  25. Yang Y, Zhu S, Li Y, et al. Human umbilical cord mesenchymal stem cells ameliorate skin fibrosis development in a mouse model of bleomycin-induced systemic sclerosis. Exp Ther Med. 2020;20(6):257.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Moroncini G, Paolini C, Orlando F, et al. Mesenchymal stromal cells from human umbilical cord prevent the development of lung fibrosis in immunocompetent mice. PLoS ONE. 2018;13(6):e0196048.

    PubMed  PubMed Central  Google Scholar 

  27. Suzuka T, Kotani T, Saito T, et al. Therapeutic effects of adipose-derived mesenchymal stem/stromal cells with enhanced migration ability and hepatocyte growth factor secretion by low-molecular-weight heparin treatment in bleomycin-induced mouse models of systemic sclerosis. Arthritis Res Ther. 2022;24(1):228.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Jin J, Ou Q, Wang Z, et al. BMSC-derived extracellular vesicles intervened the pathogenic changes of scleroderma in mice through miRNAs. Stem Cell Res Ther. 2021;12(1):327.

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Li M, Zhang HP, Wang XY, et al. Mesenchymal stem cell-derived exosomes ameliorate dermal fibrosis in a murine model of bleomycin-induced scleroderma. Stem Cells Dev. 2021;30(19):981–90.

    CAS  PubMed  Google Scholar 

  30. Maria AT, Toupet K, Bony C, et al. Antifibrotic, antioxidant, and immunomodulatory effects of mesenchymal stem cells in HOCl-induced systemic sclerosis. Arthritis Rheumatol (Hoboken, NJ). 2016;68(4):1013–25.

    CAS  Google Scholar 

  31. Maria ATJ, Toupet K, Maumus M, et al. Fibrosis development in HOCl-induced systemic sclerosis: a multistage process hampered by mesenchymal stem cells. Front Immunol. 2018;9:2571.

    PubMed  PubMed Central  Google Scholar 

  32. Jin X, Hou J, Zheng K, et al. Umbilical cord mesenchymal stem cells for inhibiting the fibrosis and autoimmune development in HOCl-induced systemic scleroderma mouse model. Int J Stem Cells. 2021;14(3):262–74.

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Elessawi DF, Gabr H, Badawy MMM, et al. Therapeutic potential of mesenchymal stem cells for scleroderma induced in mouse model. Tissue Cell. 2021;73:101671.

    CAS  PubMed  Google Scholar 

  34. Maria AT, Toupet K, Maumus M, et al. Human adipose mesenchymal stem cells as potent anti-fibrosis therapy for systemic sclerosis. J Autoimmun. 2016;70:31–9.

    CAS  PubMed  Google Scholar 

  35. Akiyama K, Chen C, Wang D, et al. Mesenchymal-stem-cell-induced immunoregulation involves FAS-ligand-/FAS-mediated T cell apoptosis. Cell Stem Cell. 2012;10(5):544–55.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Chen C, Wang D, Moshaverinia A, 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):559–77.

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Lim JY, Ryu DB, Lee SE, et al. Mesenchymal stem cells (MSCs) attenuate cutaneous sclerodermatous graft-versus-host disease (Scl-GVHD) through inhibition of immune cell infiltration in a mouse model. J Invest Dermatol. 2017;137(9):1895–904.

    CAS  PubMed  Google Scholar 

  38. Okamura A, Matsushita T, Komuro A, et al. Adipose-derived stromal/stem cells successfully attenuate the fibrosis of scleroderma mouse models. Int J Rheum Dis. 2020;23(2):216–25.

    CAS  PubMed  Google Scholar 

  39. Zhao F, Zhang YF, Liu YG, et al. Therapeutic effects of bone marrow-derived mesenchymal stem cells engraftment on bleomycin-induced lung injury in rats. Transplant Proc. 2008;40(5):1700–5.

    CAS  Google Scholar 

  40. Moodley Y, Atienza D, Manuelpillai U, et al. Human umbilical cord mesenchymal stem cells reduce fibrosis of bleomycin-induced lung injury. Am J Pathol. 2009;175(1):303–13.

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Wu Y, Huang S, Enhe J, et al. Bone marrow-derived mesenchymal stem cell attenuates skin fibrosis development in mice. Int Wound J. 2014;11(6):701–10.

    PubMed  Google Scholar 

  42. Yamamoto T, Takagawa S, Katayama I, et al. Animal model of sclerotic skin. I: Local injections of bleomycin induce sclerotic skin mimicking scleroderma. J Invest Dermatol. 1999;112(4):456–62.

    CAS  PubMed  Google Scholar 

  43. Beyer C, Schett G, Distler O, et al. Animal models of systemic sclerosis: prospects and limitations. Arthritis Rheum. 2010;62(10):2831–44.

    CAS  PubMed  Google Scholar 

  44. Cahill EF, Kennelly H, Carty F, et al. Hepatocyte growth factor is required for mesenchymal stromal cell protection against bleomycin-induced pulmonary fibrosis. Stem Cells Transl Med. 2016;5(10):1307–18.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Sakiyama R, Fukuta K, Matsumoto K, et al. Stimulation of hepatocyte growth factor production by heparin-derived oligosaccharides. J Biochem. 2007;141(5):653–60.

    CAS  PubMed  Google Scholar 

  46. Servettaz A, Goulvestre C, Kavian N, et al. Selective oxidation of DNA topoisomerase 1 induces systemic sclerosis in the mouse. J Immunol. 2009;182(9):5855–64.

    CAS  PubMed  Google Scholar 

  47. Green MC, Sweet HO, Bunker LE. Tight-skin, a new mutation of the mouse causing excessive growth of connective tissue and skeleton. Am J Pathol. 1976;82(3):493–512.

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Jagasia MH, Greinix HT, Arora M, et al. National institutes of health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. The 2014 diagnosis and staging working group report. Biol Blood Marrow Transplant. 2015;21(3):389-401.e1.

    PubMed  Google Scholar 

  49. Jaffee BD, Claman HN. Chronic graft-versus-host disease (GVHD) as a model for scleroderma. I. Description of model systems. Cell Immunol. 1983;77(1):1–12.

    CAS  PubMed  Google Scholar 

  50. Yang X, Liu C, Fujino M, et al. A modified graft-versus-host-induced model for systemic sclerosis, with pulmonary fibrosis in Rag2-deficient mice. FEBS Open Bio. 2017;7(9):1316–27.

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Claman HN, Jaffee BD, Huff JC, et al. Chronic graft-versus-host disease as a model for scleroderma. II. Mast cell depletion with deposition of immunoglobulins in the skin and fibrosis. Cell Immunol. 1985;94(1):73–84.

    CAS  PubMed  Google Scholar 

  52. Christopeit M, Schendel M, FöLL J, et al. Marked improvement of severe progressive systemic sclerosis after transplantation of mesenchymal stem cells from an allogeneic haploidentical-related donor mediated by ligation of CD137L. Leukemia. 2008;22(5):1062–4.

    CAS  PubMed  Google Scholar 

  53. Keyszer G, Christopeit M, Fick S, et al. Treatment of severe progressive systemic sclerosis with transplantation of mesenchymal stromal cells from allogeneic related donors: report of five cases. Arthritis Rheum. 2011;63(8):2540–2.

    PubMed  Google Scholar 

  54. Guiducci S, Porta F, Saccardi R, et al. Autologous mesenchymal stem cells foster revascularization of ischemic limbs in systemic sclerosis: a case report. Ann Intern Med. 2010;153(10):650–4.

    PubMed  Google Scholar 

  55. Scuderi N, Ceccarelli S, Onesti MG, et al. Human adipose-derived stromal cells for cell-based therapies in the treatment of systemic sclerosis. Cell Transplant. 2013;22(5):779–95.

    PubMed  Google Scholar 

  56. Wehbe T, Abi Saab M, Abi Chahine N, et al. Mesenchymal stem cell therapy for refractory scleroderma: a report of 2 cases. Stem Cell Investig. 2016;3:48.

    PubMed  PubMed Central  Google Scholar 

  57. Zhang H, Liang J, Tang X, et al. Sustained benefit from combined plasmapheresis and allogeneic mesenchymal stem cells transplantation therapy in systemic sclerosis. Arthritis Res Ther. 2017;19(1):165.

    PubMed  PubMed Central  Google Scholar 

  58. Wang J, Cai J, Zhang Q, et al. Fat transplantation induces dermal adipose regeneration and reverses skin fibrosis through dedifferentiation and redifferentiation of adipocytes. Stem Cell Res Ther. 2022;13(1):499.

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Cras A, Farge D, Carmoi T, et al. Update on mesenchymal stem cell-based therapy in lupus and scleroderma. Arthritis Res Ther. 2015;17:301.

    PubMed  PubMed Central  Google Scholar 

  60. Czirják L, Foeldvari I, Müller-Ladner U. Skin involvement in systemic sclerosis. Rheumatology (Oxford). 2008;47(5):v44–5.

    PubMed  Google Scholar 

  61. Cui J, Jin L, Ding M, et al. Efficacy and safety of mesenchymal stem cells in the treatment of systemic sclerosis: a systematic review and meta-analysis. Stem Cell Res Ther. 2022;13(1):118.

    PubMed  PubMed Central  Google Scholar 

  62. Volarevic V, Markovic BS, Gazdic M, et al. Ethical and safety issues of stem cell-based therapy. Int J Med Sci. 2018;15(1):36–45.

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Varderidou-Minasian S, Lorenowicz MJ. Mesenchymal stromal/stem cell-derived extracellular vesicles in tissue repair: challenges and opportunities. Theranostics. 2020;10(13):5979–97.

    CAS  PubMed  PubMed Central  Google Scholar 

  64. van Niel G, D’Angelo G, Raposo G. Shedding light on the cell biology of extracellular vesicles. Nat Rev Mol Cell Biol. 2018;19(4):213–28.

    PubMed  Google Scholar 

  65. Keshtkar S, Azarpira N, Ghahremani MH. Mesenchymal stem cell-derived extracellular vesicles: novel frontiers in regenerative medicine. Stem Cell Res Ther. 2018;9(1):63.

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Rozier P, Maumus M, Bony C, et al. Extracellular vesicles are more potent than adipose mesenchymal stromal cells to exert an anti-fibrotic effect in an in vitro model of systemic sclerosis. Int J Mol Sci. 2021;22(13):6834.

    Google Scholar 

  67. Phinney DG, Pittenger MF. Concise review: MSC-derived exosomes for cell-free therapy. Stem Cells. 2017;35(4):851–8.

    CAS  PubMed  Google Scholar 

  68. Milbank E, Dragano NRV, González-García I, et al. Small extracellular vesicle-mediated targeting of hypothalamic AMPKα1 corrects obesity through BAT activation. Nat Metab. 2021;3(10):1415–31.

    CAS  PubMed  Google Scholar 

  69. Zhuang WZ, Lin YH, Su LJ, et al. Mesenchymal stem/stromal cell-based therapy: mechanism, systemic safety and biodistribution for precision clinical applications. J Biomed Sci. 2021;28(1):28.

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Herrmann IK, Wood MJA, Fuhrmann G. Extracellular vesicles as a next-generation drug delivery platform. Nat Nanotechnol. 2021;16(7):748–59.

    CAS  PubMed  Google Scholar 

  71. Rockel JS, Rabani R, Viswanathan S. Anti-fibrotic mechanisms of exogenously-expanded mesenchymal stromal cells for fibrotic diseases. Semin Cell Dev Biol. 2020;101:87–103.

    PubMed  Google Scholar 

  72. Rozier P, Maumus M, Maria ATJ, et al. Lung fibrosis Is improved by extracellular vesicles from IFNγ-primed mesenchymal stromal cells in murine systemic sclerosis. Cells. 2021;10(10):2727.

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Rozier P, Maumus M, Maria ATJ, et al. Mesenchymal stromal cells-derived extracellular vesicles alleviate systemic sclerosis via miR-29a-3p. J Autoimmun. 2021;121:102660.

    CAS  PubMed  Google Scholar 

  74. Baral H, Uchiyama A, Yokoyama Y, et al. Antifibrotic effects and mechanisms of mesenchymal stem cell-derived exosomes in a systemic sclerosis mouse model: possible contribution of miR-196b-5p. J Dermatol Sci. 2021;104(1):39–47.

    CAS  PubMed  Google Scholar 

  75. Yu Y, Shen L, Xie X, et al. The therapeutic effects of exosomes derived from human umbilical cord mesenchymal stem cells on scleroderma. Tissue Eng Regen Med. 2022;19(1):141–50.

    CAS  PubMed  Google Scholar 

  76. Guo L, Lai P, Wang Y, et al. Extracellular vesicles derived from mesenchymal stem cells prevent skin fibrosis in the cGVHD mouse model by suppressing the activation of macrophages and B cells immune response. Int Immunopharmacol. 2020;84:106541.

    CAS  PubMed  Google Scholar 

  77. Hostettler KE, Gazdhar A, Khan P, et al. Multipotent mesenchymal stem cells in lung fibrosis. PLoS ONE. 2017;12(8):e0181946.

    PubMed  PubMed Central  Google Scholar 

  78. Toledo DM, Pioli PA. Macrophages in systemic sclerosis: novel insights and therapeutic implications. Curr Rheumatol Rep. 2019;21(7):31.

    PubMed  PubMed Central  Google Scholar 

  79. Sarvar DP, Effatpanah H, Akbarzadehlaleh P, et al. Mesenchymal stromal cell-derived extracellular vesicles: novel approach in hematopoietic stem cell transplantation. Stem Cell Res Ther. 2022;13(1):202.

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors acknowledge the support from the National Natural Science Foundation of China (No. 81871277) and innovative research team of high-level local universities in Shanghai-Clinical and basic research on the prevention and treatment of some inflammatory diseases by integrative medicine.

Funding

This study was supported by the National Natural Science Foundation of China (No. 81871277) and innovative research team of high-level local universities in Shanghai-Clinical and basic research on the prevention and treatment of some inflammatory diseases by integrative medicine.

Author information

Authors and Affiliations

  1. Department of Rheumatology, Huashan Hospital, Fudan University, Shanghai, China

    Yu Xiao, Zhongzhou Huang, Yingyu Wang, Weiguo Wan, Hejian Zou & Xue Yang

  2. Institute of Rheumatology, Immunology and Allergy, Fudan University, Shanghai, China

    Yu Xiao, Zhongzhou Huang, Yingyu Wang, Weiguo Wan, Hejian Zou & Xue Yang

  3. Department of Dermatology, Zhongshan Hospital, Fudan University, Shanghai, China

    Ji Yang

Authors
  1. Yu Xiao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zhongzhou Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yingyu Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ji Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Weiguo Wan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hejian Zou
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Xue Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

These authors contributed equally: YX, ZH and YW. All authors read and approved the final version.

Corresponding authors

Correspondence to Hejian Zou or Xue Yang.

Ethics declarations

Competing interests

The authors declare that they have no competing interests.

Ethics approval and consent to participate

Not applicable.

Consent for publication

All of the authors approved the manuscript for publication.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Xiao, Y., Huang, Z., Wang, Y. et al. Progress in research on mesenchymal stem cells and their extracellular vesicles for treating fibrosis in systemic sclerosis. Clin Exp Med 23, 2997–3009 (2023). https://doi.org/10.1007/s10238-023-01136-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10238-023-01136-8

Keywords

Search

Navigation