人胎盘间充质干细胞及诱导的胰岛样细胞移植治疗妊娠期糖尿病大鼠效果比较  

Comparison on the curative effect of human placenta-derived mesenchymal stem cells and induced islet-like cells in gestational diabetes mellitus rats

作　　者：高珊[1] 黄东静[1] 洪海漫[1] 贾京桥 孟斐[1] Gao Shan;Huang Dongjing;Hong Haiman;Jia Jingqiao;Meng Fei(Department of Obstetrics,Affiliated Central Hospital of Shenyang Medical College,Shenyang 110024,Liaoning Province,China;WellCare Stem Cell Biotech(Liaoning)Co.,Ltd.,Benxi 110024,Liaoning Province,China)

机构地区：[1]沈阳医学院附属中心医院产科,辽宁省沈阳市110024 [2]唯尔克干细胞生物科技(辽宁)有限公司,辽宁省本溪市110024

出　　处：《中国组织工程研究》2021年第25期3981-3987,共7页Chinese Journal of Tissue Engineering Research

基　　金：沈阳医学院科技基金(20182040),项目负责人:高珊;沈阳市卫生和计划生育委员会科研项目,项目负责人:高珊。

摘　　要：背景:妊娠期糖尿病易对孕产妇和胎儿的健康造成严重损害,探索安全有效的妊娠期糖尿病预防和治疗手段成为妇产科学的重要研究方向之一。目的:对比人胎盘间充质干细胞和胰岛样细胞对妊娠期糖尿病大鼠的治疗效果,为其用于临床研究治疗妊娠期糖尿病提供理论依据。方法:在无菌条件下提取人胎盘组织中的人胎盘间充质干细胞,将其诱导分化为胰岛样细胞,采用流式细胞术检测分化过程中巢蛋白和胰岛素的表达,采用双硫腙染色法检测胰岛样细胞团中锌离子表达。将雌性SD大鼠随机分为5组:正常孕鼠组、妊娠期糖尿病鼠未干预组、妊娠期糖尿病鼠生理盐水干预组、妊娠期糖尿病鼠人胎盘间充质干细胞干预组、妊娠期糖尿病鼠胰岛样细胞干预组,每组10只。采用妊娠前喂食高糖高脂饮食和妊娠后腹腔注射链脲佐菌素的方法建立妊娠期糖尿病模型,建模成功后,尾静脉注射1 mL含6×106个人胎盘间充质干细胞或胰岛样细胞的生理盐水悬液,分别于妊娠第6,12,18天检测各组孕鼠体质量和空腹血糖,妊娠第18天检测孕鼠血清脂联素水平。结果与结论:①在人胎盘间充质干细胞诱导分化为胰岛样细胞过程中,胰岛素水平逐渐增高;巢蛋白表达水平先上升后逐渐下降;在诱导分化的第28天形成胰岛样细胞团;②人胎盘间充质干细胞和胰岛样细胞均能使妊娠期糖尿病鼠血糖降低,体质量升高,脂联素水平升高;妊娠第18天,与人胎盘间充质干细胞干预组相比,胰岛样细胞干预组大鼠体质量上升、血糖降低、脂联素水平升高效果更明显;③结果表明,人胎盘间充质干细胞和胰岛样细胞均能有效治疗妊娠期糖尿病鼠,由人胎盘间充质干细胞诱导分化的胰岛样细胞治疗效果更优。BACKGROUND:Gestational diabetes can cause serious damage to maternal and fetal health.Exploring safe and effective methods on gestational diabetes prevention and treatment has become one of the important research directions of obstetrics and gynecology.OBJECTIVE:To compare the therapeutic effects of human placenta-derived mesenchymal stem cells and islet-like cells on gestational diabetes mellitus rats,so as to provide theoretical basis for clinical research on the treatment of gestational diabetes mellitus.METHODS:Human placenta-derived mesenchymal stem cells were extracted from human placental tissue under aseptic conditions,then the identified stem cells were induced into islet-like cells.Flow cytometry was used to detecte the expressions of insulin and nestin protein in differentiated cells and dithizone staining was used to identify the expression of zinc ions in islet-like cell clusters.Female Sprague-Dawley rats were divided into five groups(n=10 per group):Normal pregnant rats group,gestational diabetes mellitus rats without intervention group,gestational diabetes mellitus rats saline intervention group,gestational diabetes mellitus rats human placenta-derived mesenchymal stem cells intervention group and gestational diabetes mellitus rats islet-like cells intervention group.Gestational diabetes mellitus model was established by feeding high-glucose and high-fat diet before pregnancy and intraperitoneal injection of streptozotocin after pregnancy.After successful modeling,1 mL normal saline suspension containing 6×106 human placenta-derived mesenchymal stem cells or islet-like cells was injected via tail vein.The fasting blood glucose and body weight of rats in each group were measured at 6,12,and 18 days of pregnancy,and the serum adiponectin level of pregnant rats was detected at 18 days of pregnancy.RESULTS AND CONCLUSION:(1)During the differentiation of human placenta-derived mesenchymal stem cells into islet-like cells,the insulin level increased and the nestin level increased then decreased gradual

关 键 词：干细胞 胎盘间充质干细胞 胰岛样细胞 诱导分化 妊娠期糖尿病 血糖 脂联素 

分 类 号：R459.9[医药卫生—治疗学] R318.5[医药卫生—临床医学]