人脐带间充质干细胞诱导的胰岛样细胞不同途径移植治疗1型糖尿病鼠

Transplantation of islet-like cells induced by human umbilical cord mesenchymal stem cells via different ways for the treatment of type 1 diabetic mice

背景:人脐带间充质干细胞诱导的胰岛样细胞移植于1型糖尿病鼠体内,会使血糖降低,糖尿病症状有所改善,但腹腔移植的方式少有报道。目的:观察不同途径移植人脐带间充质干细胞诱导的胰岛样细胞对于1型糖尿病小鼠的治疗效果。方法:选采用组织块贴壁法分离培养人脐带间充质干细胞,然后将其定向分化为胰岛样细胞。从15只雄性C57BL/6J小鼠中随机取3只小鼠做正常组,其余12只小鼠腹腔注射链脲佐菌素制备1型糖尿病模型。造模成功9只小鼠随机分为糖尿病组、尾静脉-胰岛样细胞组、腹腔-胰岛样细胞组,每组3只。造模10 d后,正常组和糖尿病组不予处理,尾静脉-胰岛样细胞组经尾静脉注射0.4 mL胰岛样细胞悬液(含5×10^5个细胞),腹腔-胰岛样细胞组经腹腔注射0.4 mL胰岛样细胞悬液(含5×10^5个细胞)。移植后每周检测2次血糖,移植后28 d进行葡萄糖耐量实验,移植后42 d检测胰岛素水平。结果与结论:①与糖尿组相比,尾静脉-胰岛样细胞组在移植后第10天开始血糖明显下降,一直维持到31 d,胰岛素水平升高,葡萄糖耐量改善,差异有显著性意义(P<0.05);腹腔-胰岛样细胞组血糖、胰岛素水平、葡萄糖耐量未见明显改善;②结果提示,应用人脐带间充质干细胞诱导的胰岛样细胞治疗1型糖尿病鼠,尾静脉注射是一种比较理想的移植方式,腹腔注射的效果不佳。

BACKGROUND:Transplanting islet-like cells induced by human umbilical cord mesenchymal stem cells(hUC-MSCs)into type 1 diabetic mice can reduce blood glucose level and improve the symptoms of diabetes mellitus.However,there are few reports on intraperitoneal transplantation.OBJECTIVE:To study the therapeutic effect of transplantation of islet-like cells induced by hUC-MSCs in different ways for the treatment of type 1 diabetic mice.METHODS:The hUC-MSCs were isolated and cultured by tissue explants adherent method and differentiated into islet-like cells.The 3 of 15 male C57BL/6J mice were used as normal group,and the remaining mice were taken to prepare a mouse model of type 1 diabetes using intraperitoneal injection of streptozotocin.After successful modeling,nine model mice were randomly divided into diabetes group,tail vein-islet-like cells group,and abdomen-islet-like cells group,with three mice in each group.After 10 days of modeling,the normal group and diabetic group were not treated.The tail vein-islet-like cells group was injected with 5×105 cells/0.4 mL islet-like cells via the tail vein and the abdomen-islet-like cells group was intraperitoneally injected with 5×105 cells/0.4 mL islet-like cells.During the treatment,the blood glucose and insulin levels were measured twice a week;glucose tolerance test was performed at 28 days after cell transplantation;and fasting insulin level was detected at 42 days after cell transplantation.RESULTS AND CONCLUSION:(1)Compared with the diabetic group,in the tail vein-islet-like cells group,the blood glucose level began to decrease on the 10th day after transplantation and maintained until the 31st day,and the insulin level and glucose tolerance significantly improved(P<0.05).However,there was no significant improvement in blood glucose level,insulin level and glucose tolerance in the abdomen-islet-like cells group.(2)To conclude,transplantation of hUCMSCs induced islet-like cells for the treatment of type 1 diabetic mice via tail vein is an ideal transplantation method,and the effect of intraperitoneal injection is unsatisfactory.