Open Access

Human umbilical cord mesenchymal stem cells ameliorate skin fibrosis development in a mouse model of bleomycin‑induced systemic sclerosis

  • Authors:
    • Yuan Yang
    • Shuai Zhu
    • Yanhong Li
    • Qian Lu
    • Qiuyi Zhang
    • Linchong Su
    • Qiuping Zhang
    • Yi Zhao
    • Yubin Luo
    • Yi Liu
  • View Affiliations

  • Published online on: October 27, 2020     https://doi.org/10.3892/etm.2020.9387
  • Article Number: 257
  • Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Mesenchymal stem cell (MSC) infusion has become a novel therapeutic strategy for complex autoimmune diseases; however, few detailed studies have been performed to investigate the benefit and mechanism of MSC treatment on systemic sclerosis (SSc). The present study aimed to evaluate the therapeutic effect of human umbilical cord derived‑MSCs (UC‑MSCs) on bleomycin‑induced SSc in mice and explore the potential underlying mechanism. The murine SSc model was established by daily subcutaneous injection of bleomycin for 4 weeks, followed with two UC‑MSC infusions every 7 days. Skin fibrosis was assessed by H&E and Masson staining. Flow cytometry was used to determine IL‑17A, IFN‑γ, tumor necrosis factor‑β, IL‑10 and IL‑12 levels in serum samples and T cell subsets in murine spleen. Additionally, gene expression levels of cytokines and fibrosis markers in skin samples were measured by reverse transcription‑quantitative PCR. Immunofluorescence staining was performed to track UC‑MSC localization and lymphocyte cell infiltration in vivo. UC‑MSC treatment exerted an anti‑fibrotic role in bleomycin‑induced SSc mice, as confirmed by histological improvement, decreased collagen synthesis, and reduced collagen‑1α1, collagen‑1α2, fibronectin‑1 and α‑smooth muscle actin gene expression levels. The results indicated that UC‑MSC treatment only had a limited systematic effect on cytokine production in serum samples and T cell activation in the spleen. By contrast, T helper (Th)17 cell infiltration and activation in skin were efficiently inhibited after UC‑MSC infusion, as evidenced by the decreased IL‑17A and retinoic acid‑related orphan receptor γt gene expression as well as IL‑17A production. UC‑MSC administration significantly ameliorated bleomycin‑induced skin fibrosis and collagen formation primarily by eliminating local inflammation and Th17 cell activation in the skin; however, the systemic inhibitory effect of UM‑MSCs on cytokines was less profound.
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December-2020
Volume 20 Issue 6

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Yang Y, Zhu S, Li Y, Lu Q, Zhang Q, Su L, Zhang Q, Zhao Y, Luo Y, Liu Y, Liu 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 20: 257, 2020
APA
Yang, Y., Zhu, S., Li, Y., Lu, Q., Zhang, Q., Su, L. ... Liu, Y. (2020). Human umbilical cord mesenchymal stem cells ameliorate skin fibrosis development in a mouse model of bleomycin‑induced systemic sclerosis. Experimental and Therapeutic Medicine, 20, 257. https://doi.org/10.3892/etm.2020.9387
MLA
Yang, Y., Zhu, S., Li, Y., Lu, Q., Zhang, Q., Su, L., Zhang, Q., Zhao, Y., Luo, Y., Liu, Y."Human umbilical cord mesenchymal stem cells ameliorate skin fibrosis development in a mouse model of bleomycin‑induced systemic sclerosis". Experimental and Therapeutic Medicine 20.6 (2020): 257.
Chicago
Yang, Y., Zhu, S., Li, Y., Lu, Q., Zhang, Q., Su, L., Zhang, Q., Zhao, Y., Luo, Y., Liu, Y."Human umbilical cord mesenchymal stem cells ameliorate skin fibrosis development in a mouse model of bleomycin‑induced systemic sclerosis". Experimental and Therapeutic Medicine 20, no. 6 (2020): 257. https://doi.org/10.3892/etm.2020.9387