Mesenchymal Stem Cell-Derived Exosomes Ameliorate Dermal Fibrosis in a Murine Model of Bleomycin-Induced Scleroderma

被引:22
作者
Li, Man [1 ]
Zhang, Hai-Ping [1 ]
Wang, Xue-Yao [2 ,3 ]
Chen, Zhi-Guo [2 ,3 ]
Lin, Xue-Fei [1 ]
Zhu, Wei [1 ]
机构
[1] Capital Med Univ, Xuanwu Hosp, Beijing Inst Geriatr, Dept Dermatol, Beijing, Peoples R China
[2] Capital Med Univ, Xuanwu Hosp, Cell Therapy Ctr, Beijing Inst Geriatr, Beijing, Peoples R China
[3] Minist Educ, Key Lab Neurodegenerat, Beijing, Peoples R China
关键词
mesenchymal stem cells; exosomes; fibrosis; scleroderma; SYSTEMIC-SCLEROSIS; PATHOGENESIS; SKIN; MYOFIBROBLAST;
D O I
10.1089/scd.2021.0112
中图分类号
Q813 [细胞工程];
学科分类号
摘要
Mesenchymal stem cells (MSCs) have become a promising therapeutic strategy for scleroderma. Exosomes derived from MSCs (MSC-exosomes) possess functional properties similar to those of their source cells. In this study, we aimed to explore the potential role of MSC-exosomes in the treatment of scleroderma. MSC-exosomes were isolated from human umbilical cords through ultracentrifugation and characterized. An experimental fibrosis model was established in BALB/c mice by a subcutaneous injection of bleomycin, followed by treatment with MSC-exosomes or MSC infusions once a week for a total of four doses. Using hematoxylin and eosin and Masson's trichrome staining and immunohistochemistry, hydroxyproline content, and quantitative real-time polymerase chain reaction analyses, we investigated the effects of MSC-exosomes on dermal fibrosis and explored the underlying mechanism. MSC-exosome treatment restored the dermal architecture, reduced dermal thickness, and partially increased subcutaneous adipose tissue thickness. In addition, MSC-exosomes inhibited the expression of collagen (COL)-I, COL-III, and alpha-smooth muscle actin. The transforming growth factor (TGF)-beta/Smad signaling pathway was also suppressed in MSC-exosome-treated mice. Taken together, our results suggest that MSC-exosomes can attenuate myofibroblast activation and collagen deposition in dermal fibrosis by downregulating the TGF-beta/Smad signaling pathway. Therefore, the use of MSC-exosomes may be a potential therapeutic approach for the treatment of scleroderma.
引用
收藏
页码:981 / 990
页数:10
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