关键词: 脂肪组织, 间质干细胞移植, 红斑狼疮, 系统性, 疾病模型, 动物, 小鼠, 近交MRL lpr

Abstract: Objective： Preliminary study on therapeutic effects of adipose tissue derived stem cells (ADSCs) on MRL/lpr mice and the effect on imbalance of Th17/Treg. Methods: Fifteen 12-week-old MRL/lpr mice were randomly divided into 3 groups by using random number table, including ADSCs group, control group and cyclophosphamide (CTX) group, with 5 in each group. ADSCs group and control group were injected with 1×106 ADSCs or phosphate buffered solution (PBS) via tail vein respectively, once a week, a total of eight times. CTX group was injected CTX at a dose of 15 mg/kg body weight, once a week for 2 weeks, and then repeated after 2 weeks’ rest, a total of four times. The 24-hour proteinuria was measured before and after treatment. All the mice were sacrificed after treatment for 8 weeks. Th17 cells and Treg cells in splenic were examined by flow cytometry. Results: (1) The 24-hour proteinuria in the three groups had no significant difference before treatment (P>0.05). After therapy for 4 weeks, the 24-hour proteinuria in the ADSCs and CTX groups was much lower than those in control group, and the difference was significant ［(5.02±1.61) g/L vs. (7.10±1.63) g/L, (4.90±0.71) g/L vs. (7.10±1.63) g/L, P<0.05］, and the longer the duration of treatment (8 weeks), the more obvious effect ［(2.24±0.73) g/L vs. (10.36±1.64) g/L, (3.80±1.45) g/L vs. (10.36±1.64) g/L, P<0.01］. There was no significant difference in 24-hour proteinuria between ADSCs group and CTX group (P>0.05). (2) Percentage of Treg cells /CD4+T cells in the spleen lymphocytes: The percentages in ADSCs and CTX groups were higher than that in control group. The levels were 13.62%±187%, 14.14%±1.29%, 10.71%±1.23%, respectively, but there was no significant difference (P>0.05). (3) Percentage of Th17 cells /CD4+T cells in the spleen lymphocytes: The percentages in ADSCs and CTX groups were significantly lower than that in control group. The levels were 1.43%±020%, 1.63%±0.65%, 6.37%±1.64%, respectively, with statistical significance (P<0.01). Conclusion: Transplantation of ADSCs can reduce the 24-hour proteinuria in MRL/lpr mice. To prolong the time of treatment, the effect is more significant. Transplantation of ADSCs can up-regulate Treg cells and down-regulate Th17 cells. ADSCs have the ability to regulate the immune balance of Th17/Treg in MRL/lpr mice, suggesting that ADSCs play the role of antiinflammatory and immune regulation by regulating the Treg and Th17 cells.

Key words: Adipose tissue, Mesenchymal stem cell transplantation, Lupus erythematosus, systemic, Disease models, animal, Mice, inbred MRL lpr