诱导性多能干细胞移植治疗小鼠系统性红斑狼疮  

Induced pluripotent stem cell transplantation for systemic lupus erythematosus in a mouse model

作　　者：马琳洁 薛文涛 谭举朋[3] Ma Linjie;Xue Wentao;Tan Jupeng(Department of Oncology,Yidu Central Hospital,Weifang 262500,Shandong Province,China;Department of Emergency,Yidu Central Hospital,Weifang 262500,Shandong Province,China;Department of Rheumatology,Yidu Central Hospital,Weifang 262500,Shandong Province,China)

机构地区：[1]潍坊市益都中心医院肿瘤内科,山东省潍坊市262500 [2]潍坊市益都中心医院急诊科,山东省潍坊市262500 [3]潍坊市益都中心医院风湿免疫科,山东省潍坊市262500

出　　处：《中国组织工程研究》2019年第33期5286-5292,共7页Chinese Journal of Tissue Engineering Research

摘　　要：背景:自体间充质干细胞的生物学特性易受疾病本身影响,寻找不受疾病影响的低免疫原性干细胞成为研究热点。目前,自体来源诱导性多能干细胞移植治疗系统性红斑狼疮尚未见报道。目的:评价自体成纤维细胞来源小鼠诱导性多能干细胞移植治疗系统性红斑狼疮的效果。方法:将54只8周龄MRL/lpr小鼠随机分为3组,模型对照组不给予干细胞注射等处理,试剂对照组尾静脉注射PBS溶液,干细胞治疗组尾静脉注射自体皮肤成纤维细胞来源诱导性多能干细胞。细胞治疗4周,ELISA法检测各组小鼠血清肌酐、尿素氮、抗双链DNA抗体和抗核抗体水平;石蜡切片苏木精-伊红染色观察小鼠肾脏组织形态结构;考马斯亮蓝法检测尿蛋白浓度;流式细胞术检测小鼠外周血调节性T细胞百分率、脾脏树突状细胞百分率、脾脏Th1/Th2比值。结果与结论:(1)与模型对照组和试剂对照组比较,干细胞治疗组血清肌酐、尿素氮、抗双链DNA抗体和抗核抗体水平降低,尿蛋白浓度降低,外周血调节性T细胞百分率、脾脏树突状细胞百分率以及脾脏Th1/Th2比值升高;(2)与模型对照组和试剂对照组比较,干细胞治疗组小鼠肾脏肾小球体积缩小,系膜细胞减少,肾小管上皮细胞变性改善,肾小管腔内管型减少;(3)上述结果说明,自体皮肤成纤维细胞来源诱导性多能干细胞移植可治疗系统性红斑狼疮小鼠,减轻肾组织损伤,改善肾功能并发挥免疫调节作用。BACKGROUND: The biological characteristics of autologous mesenchymal stem cells for transplantation ofsystemic lupus erythematosus (SLE) are susceptible to the disease. Cell therapy with low immunogenic stemcells that are not affected by the disease has become a research hotspot. To date, treatment of systemic lupuserythematosus with autologous induced pluripotent stem cell transplantation has not been reported.OBJECTIVE: To evaluate the therapeutic effect of transplantation of induced pluripotent stem cells derived from autologous fibroblasts inmice with systemic lupus erythematosus.METHODS: Fifty-four 8-week-old MRL/lpr mice were randomly divided into three groups. Model control group was not treated, reagent controlgroup was injected with PBS solution through tail vein, and stem cell treatment group was injected with autologous induced pluripotent stemcells through tail vein. Serum creatinine, urea nitrogen, anti-double-stranded DNA antibodies and anti-nuclear antibodies were detected byELISA at 4 weeks of cell treatment. Kidney tissue morphology was observed by hematoxylin-eosin staining on paraffin sections. Urinaryprotein concentrations were detected by Coomassie brilliant blue method. Flow cytometry was used to detect the percentage of regulatory Tcells in peripheral blood, percentage of splenic dendritic cells, and ratio of splenic helper T1 cells to helper T2 cells.RESULTS AND CONCLUSION: The levels of serum creatinine, urea nitrogen, anti-double-stranded DNA antibody and anti-nuclear antibodyin the stem cell treatment group were lower than those in the model control and reagent control groups, while decreased urine proteinconcentration, increased percentages of regulatory T cells in peripheral blood, increased percentage of splenic dendritic cells, and increasedsplenic Th1/Th2 ratio were detected in the stem cell treatment group as compared with the other two groups. Compared with the model controland reagent control groups, there was decreased glomerular volume, reduced number of mesangial cells, degen

关 键 词：诱导性多能干细胞 系统性红斑狼疮 干细胞移植 体细胞重编程 肾脏 免疫功能 调节性T细胞 

分 类 号：R459.9[医药卫生—治疗学] R394.2[医药卫生—临床医学]