人脐带间充质干细胞诱导分化不同阶段的胰岛样细胞移植治疗糖尿病  

Transplantation of islet-like cells from human umbilical cord mesenchymal stem cells at different induced stages for the treatment of diabetic mellitus

作　　者：山霞 崔晓兰[2] 时瀚 申义 王嘉 张社毅 郭波 王意忠 Shan Xia;Cui Xiao-lan;Shi Han;Shen Yi;Wang Jia;Zhang She-yi;Guo Bo;Wang Yi-zhong(Department of Hematology and Endocrinology, Peking University Aerospace School of Clinical Medicine, Beijing 100049,China;Pharmacology Laboratory, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China)

机构地区：[1]北京大学航天临床医学院血液内分泌科,北京市100049 [2]中国中医科学院中药研究所药理室,北京市100700

出　　处：《中国组织工程研究》2017年第29期4703-4708,共6页Chinese Journal of Tissue Engineering Research

基　　金：北京大学航天临床医学院科研基金资助项目(201302)~~

摘　　要：背景:实验室前期已对人脐带间充质干细胞进行不同时期的体外定向诱导,使其成功分化为胰岛样细胞,并检测到胰岛素表达。目的:观察人脐带间充质干细胞诱导分化不同阶段的胰岛样细胞在糖尿病大鼠模型体内的治疗效果,探索体外诱导的最佳时长。方法:将第3代人脐带间充质干细胞在体外定向诱导7,14,21,28 d使其分化为胰岛样细胞。选用清洁级健康Wistar大鼠80只,取8只做正常对照组,其余72只造模成功后,随机分为6组,分别为模型对照组、未诱导组、诱导7 d组、诱导14 d组、诱导21 d组、诱导28 d组。造模10 d后,分别经尾静脉移植相应的细胞悬液2 mL/只(细胞数量2×10~6个)。正常对照组和模型对照组经尾静脉注射不含任何细胞的培养液2 mL/只。每2周移植1次,共移植2次。治疗过程中检测各组大鼠的血糖、体质量、血清胰岛素水平,第2次细胞移植4周后处死大鼠,观察各脏器组织病理变化。结果与结论:①与模型对照组相比,各治疗组体质量上升,血糖下降,胰岛素水平升高,差异有显著性意义(P<0.05),且诱导28 d组治疗效果最佳;②各治疗组病理切片显示,肝脏和肾脏组织结构清晰,未发生坏死、纤维化等异常改变;③实验结果表明,人脐带间充质干细胞诱导不同阶段的胰岛样细胞移植治疗糖尿病安全有效,体外诱导28 d的胰岛样细胞治疗效果最为显著。BACKGROUND:In previous studies,the human umbilical cord mesenchymal stem cells(hUC-MSCs)have beensuccessfully differentiated into islet-like cells in vitro,and insulin expressions have been found.OBJECTIVE:To compare the therapeutic effects of different induced stages of islet-like cells differentiated fromhUC-MSCs in a diabetic rat in vivo,so as to find the most suitable induced time in vitro and provide a theoretical basis forclinical treatment of diabetes mellitus.METHODS:Passage3hUC-MSCs were differentiated into islet-like cells after7,14,21,28days of oriented induction.Eighty male healthy Wistar rats,clean grade,were used in the study.Except eight rats in normal control group,all therats were injected with streptozotocin at a dose of70mg/kg to establish diabetic models.The rats at10days aftersuccessful modeling were randomly divided into model control group,non-induced group,7-day induction group,14-dayinduction group,21-day induction group and28-day induction group.Rats in the normal control group and model controlgroup were given2mL of culture medium without any cells and rats in the other groups were implanted withcorresponding cell suspension(2×106cells)via tail vein for two sessions with an interval of2weeks.The blood glucoselevel,body mass and serum insulin level were detected during the treatment process.The rats were executed to observethe structure changes of each organ at4weeks after the second cell transplantation.RESULTS AND CONCLUSION:(1)Compared with the model control group,the body mass and the serum insulin levelsignificantly increased and the blood glucose levels significantly decreased in all the transplantation groups(P<0.05),and the therapeutic effect was best in the28-day induction group.(2)Compared with the model control group and normalcontrol group,the frozen sections in all the transplantation groups showed that the morphological structures of the liverand kidney were clear with no abnormal changes,such as necrosis and fibrosis,after transplantation.Theseexperimental results show th

关 键 词：糖尿病 脐带 间质干细胞 细胞分化 胰岛素分泌细胞 组织工程 

分 类 号：R394.2[医药卫生—医学遗传学]