Effects of adipose-derived mesenchymal stem cells on fibroblast proliferation in mouse scleroderma lesions and underlying mechanisms

doi:10.3969/j.issn.2095-4344.0657

Abstract

Abstract:

BACKGROUND: Adipose-derived mesenchymal stem cells (ADSCs) maintain the potential of multidirectional differentiation during long-term culture in vitro, and can secrete various anti-fibrotic cytokines or growth factors that are involved in regulating fibroblast proliferation and inhibiting collagen deposition, and thereby exert anti-fibrotic effects.
OBJECTIVE: To investigate the effects of ADSCs on the proliferation and apoptosis of fibroblasts in scleroderma mice and to explore the underlying mechanisms.
METHODS: Fibroblasts were isolated and purified from the skin tissue of scleroderma mice. After passage, the cells were divided into five groups according to different treatment methods: control group, ADSCs intervention group, Wnt inhibitor HY-15597 treatment group (Wnt inhibitor group), Wnt activator SB-216763 treatment group (Wnt activator group), ADSCs+SB-216763 treatment group (combined group). Cell proliferation rate and apoptosis rate were detected using MTT and flow cytometry. The levels of collagen type I, collagen type III, and Wnt signaling pathway related proteins were detected and compared.
RESULTS AND CONCLUSION: Compared with the control group, the proliferation rate of fibroblasts in the ADSCs intervention group and Wnt inhibitor group decreased and the apoptotic rate of fibroblasts increased significantly, while the proliferation rate increased and the apoptosis rate decreased in the Wnt activator group in a time-dependent manner (P < 0.05). Compared with the Wnt activator group, the proliferation rate of fibroblasts in the combined group was significantly lowered and the apoptotic rate was significantly increased (P < 0.05). Compared with the control group, the expression of hydroxyproline, collagen type I, collagen type III, Wnt2, Wnt3a, and β-catenin in the fibroblasts of ADSCs intervention group and Wnt inhibitor group were significantly decreased, while those in the Wnt activator group were significantly increased (P < 0.05). The levels of hydroxyproline, collagen type I, collagen type III, Wnt2, Wnt3a, and β-catenin in the combined group were significantly lower than those in the Wnt activator group (P < 0.05). The overall results indicate that ADSCs can inhibit the proliferation and collagen deposition of fibroblasts in the lesion tissue of mouse scleroderma models by inhibition of the Wnt/β-catenin signaling pathway.

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

Key words: Skin and Connective Tissue Diseases, Fibroblasts, Adipose Tissue, Mesenchymal Stem Cells, Wnt Proteins, Tissue Engineering

CLC Number:

R394.2

Wang Wei, Huang Yu-cheng, Chen Yan-hui. Effects of adipose-derived mesenchymal stem cells on fibroblast proliferation in mouse scleroderma lesions and underlying mechanisms[J]. Chinese Journal of Tissue Engineering Research, 2018, 22(33): 5249-5254.

Figures/Tables 7

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