Chinese Journal of Tissue Engineering Research ›› 2021, Vol. 25 ›› Issue (13): 2011-2017.doi: 10.3969/j.issn.2095-4344.3512

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Therapeutic mechanism of adipose mesenchymal stem cells in mice with systemic sclerosis

Zhang Jingying1, Sun Xiaolin2, Geng Lixia1   

  1. 1Department of Intensive Medicine, First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science & Technology, Baotou 014010, Inner Mongolia Autonomous Region, China; 2Key Autoimmunity Laboratory of Inner Mongolia, Institute of Rheumatology, Department of Rheumatology, First Affiliated Hospital of Baotou Medical College, Baotou 014010, Inner Mongolia Autonomous Region, China
  • Received:2020-05-27 Revised:2020-05-28 Accepted:2020-06-17 Online:2021-05-08 Published:2020-12-28
  • Contact: Geng Lixia, Chief physician, Master’s supervisor, Department of Intensive Medicine, First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science & Technology, Baotou 014010, Inner Mongolia Autonomous Region, China Sun Xiaolin, MD, Key Autoimmunity Laboratory of Inner Mongolia, Institute of Rheumatology, Department of Rheumatology, First Affiliated Hospital of Baotou Medical College, Baotou 014010, Inner Mongolia Autonomous Region, China
  • About author:Zhang Jingying, Master candidate, Department of Intensive Medicine, First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science & Technology, Baotou 014010, Inner Mongolia Autonomous Region, China
  • Supported by:
    the National Natural Science Foundation of China, No. 81860294 (to SXL); the Natural Science Foundation Project of Inner Mongolia Autonomous Region, No. 2019MS08055 (to SXL); the Science and Technology Planning Project of Inner Mongolia Autonomous Region, No. 201802089 (to GLX)

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Abstract: BACKGROUND: Although clinical studies have found that autologous adipose mesenchymal stem cells can effectively reduce facial fibrosis in patients with radiation-induced systemic sclerosis, but the mechanism of action has not been thoroughly analyzed. 
OBJECTIVE: To study the mechanism of action of adipose mesenchymal stem cells on bleomycin-induced systemic sclerosis in mice. 
METHODS:  Forty SPF C57BL/6J female mice aged 6-8 weeks were randomly assigned to normal control group, adipose mesenchymal stem cells group, bleomycin group, and PBS group. Mice in the latter three groups were subjected to subcutaneous injection with bleomycin every other day for 28 days, and mouse models of systemic sclerosis were established. After successful model establishment, mice in the adipose mesenchymal stem cells group were subcutaneously injected with adipose mesenchymal stem cells; mice in the PBS group were subcutaneously injected with PBS; the treatments lasted for 14 days. Enzyme-linked immunosorbent assay was used to determine the levels of serum interleukin-17, transforming growth factor-β, interleukin-6, and tumor necrosis factor-α. Hematoxylin-eosin staining and Masson staining were utilized to measure histopathological changes in the skin and lung of systemic sclerosis mice. Immunofluorescence method was applied to examine collagen I, III, and V and CD31 expression levels in the skin and lung. 
RESULTS AND CONCLUSION: (1) Compared with the bleomycin group, the expression levels of interleukin-17, transforming growth factor-β, interleukin-6, and tumor necrosis factor-α were significantly decreased in the adipose mesenchymal stem cells group (P < 0.01). (2) Compared with the normal control group, the skin dermis of mice was thickened; inflammatory cells infiltrated; skin appendages reduced; the alveoli were atrophic and collapsed; with a lot of inflammatory cell infiltration, pulmonary arteriole wall thickening, microvascular basement membrane thickening, and fibrinoid necrosis, and the inflammatory symptoms improved after treatment in the adipose mesenchymal stem cells group. (3) Compared with the normal control group, the skin and lung tissues of bleomycin group mice showed a large aggregation of collagen fibers, and the collagen fibers were reduced after adipose mesenchymal stem cells treatment. (4) After treatment with adipose mesenchymal stem cells, the expression levels of collagen I, III, and V were decreased in the skin and lung tissue of mice, but the expression of CD31 in the skin tissues was increased in the bleomycin group (P < 0.01). (5) The results suggested that adipose mesenchymal stem cells can regulate the immune response of bleomycin mice and reduce fibrosis, inflammation and vascular lesions.


Key words: stem cells, adipose mesenchymal stem cells, anti-inflammatory, anti-fibrotic, immunoreaction, systemic sclerosis, mice, experiment

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