人脐带间充质干细胞对猕猴糖尿病治疗效果的研究

Safety and efficacy of human umbilical cord mesenchymal stem cells for diabetes in macaques

目的通过用人脐带间充质干细胞(huMSCs)治疗猕猴糖尿病模型观察其血糖的变化。方法猕猴9只,分为对照组3只和模型组6只,模型组通过高糖高脂饮食及静脉注射链尿佐菌素(STZ)诱导成糖尿病模型,两组间比较用t检验。12周时再分为模型对照组3只和治疗组3只,治疗组每只每周静脉回输huMSCs 1×10~6个/kg,连续3周,每周检测各组血糖变化,三组间比较用方差分析。结果两组猕猴高糖高脂饮食喂养第8周时模型组空腹血糖值[(22.00±3.00)mmol/L]与对照组[(4.75±0.20)mmol/L]相比差异有统计学意义(t=9.94,P<0.01)。40周时1只猕猴因糖尿病死亡,病理切片证实心、肝、脾、肺、肾和胰腺均有病变,符合糖尿病特征。huMSCs治疗后,3周血糖连续下降,到第4周对照组、模型组、治疗组空腹血糖分别为(4.85±0.35)mmol/L、(18.20±1.00)mmol/L、(4.09±0.50)mmol/L,3组差异有统计学意义(F=388.10,P<0.01)。两两比较结果表明对照组和模型组比较差异有统计学意义(t=24.173,P<0.01),模型组与治疗组比较差异有统计学意义(t=25.549,P=0.014)。结论 STZ联合高糖高脂饲料能成功诱导出猕猴糖尿病模型,用huMSCs能有效降低血糖,使糖尿病猕猴恢复正常血糖,方法简便。

Objective To evaluate the safety and efficacy of human umbilical cord mesenchymal stem cells （huMSCs） in the macaque model of diabetes. Methods Nine macaques were divided into either control group （n = 3） or model group （n = 6）. Diabetes was induced by high-sugar, high-fat diet and intravenous injection of streptozotocin （STZ）. Comparison between the two groups was performed using t test. At 12 weeks diabetic macaques were subdivided into the model control group （n = 3 ） and the treatment group （n = 3 ）, and the treatment group was given weekly intravenous transfusion of 1 × 10^6 huMSCs per kilogram of body weight for 3 weeks. Blood sugar levels were measured weekly. Comparison among the three groups was performed using variance analysis. Results At the 8th week, the fasting blood glucose level increased significantly in the model group （22.00±3.00） mmol/L. Compared with the control group （4.89±0.16） mmol/L, the difference was statistically significant （t = 9.94, P 〈 0.01 ）. A monkey died due to diabetes at 40 weeks. Pathological examination showed heart, liver, spleen, lungs, kidneys and pancreas had the characteristics of diabetes. After huMSCs therapy, blood sugar continuously declined for 3 weeks. At the fourth week, the fasting blood glucose of the control group, the model group and the treatment group were 4.85±0.35 mmol/L, 18.20 ±1.00 mmol/L, and 4.09 ± 0.50 mmol/L respectively. There was significant difference between the control group and the model group （t = 24.173, P 〈 0.01 ）, and between the model group and the treatment group （t = 25.549, P = 0.014）. Conclusion STZ and high-sugar, high-fat diet can induce diabetes in macaques. HuMSCs is simple and effective in treating diabetes.