Adipose tissue derived stem cells' treatment effects in MRL/lpr mice and its effects on the imbalance of Th17/Treg cells / 北京大学学报(医学版)

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 × 106ADSCs 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 lymphocytesThe 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 lymphocytesThe 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.