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

被引：15

作者：

Yang, Yuan ^{[1
,2
]}

Zhu, Shuai ^{[1
]}

Li, Yanhong ^{[1
]}

Lu, Qian ^{[3
]}

Zhang, Qiuyi ^{[1
]}

Su, Linchong ^{[1
]}

Zhang, Qiuping ^{[1
]}

Zhao, Yi ^{[1
]}

Luo, Yubin ^{[1
]}

Liu, Yi ^{[1
]}

机构：

[1] Sichuan Univ, West China Hosp, Dept Rheumatol, 37 Guoxue Xiang, Chengdu 610041, Sichuan, Peoples R China

[2] Chengdu Med Coll, Affiliated Hosp 1, Dept Rheumatol & Immunol, Chengdu 610500, Sichuan, Peoples R China

[3] Nanjing Univ, Coll Engn & Appl Sci, Dept Biomed Engn, Nanjing 210023, Jiangsu, Peoples R China

来源：

EXPERIMENTAL AND THERAPEUTIC MEDICINE | 2020年 / 20卷 / 06期

基金：

国家重点研发计划;

关键词：

bleomycin-induced systemic sclerosis; mesenchymal stem cell; T helper 17 cell; interleukin-17A; GROWTH-FACTOR-BETA; GENE-EXPRESSION; PERIPHERAL-BLOOD; INTERFERON-GAMMA; STROMAL CELLS; LUNG INJURY; FIBROBLASTS; PATHOGENESIS; ASSOCIATION; ENGRAFTMENT;

D O I：

10.3892/etm.2020.9387

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

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-gamma, tumor necrosis factor-beta, 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-1 alpha 1, collagen-1 alpha 2, fibronectin-1 and alpha -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 gamma t 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.

引用

页数：10

共 79 条

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