PDX-1基因转染人脂肪间充质干细胞向胰岛样细胞分化及移植治疗1型糖尿病

摘要

BACKGROUND:Recent studies have shown that adipose-derived mesenchymal stem cells (ADMSCs) not only have multilineage differentiation potential, but also exert an important role in blood sugar balance and hormone production.OBJECTIVE:To observe the differentiation potential of human ADMSCs (hADMSCs) into functional islet-like cells and the therapeutic effect of hADMSCs transplantation in diabetic rats.METHODS:PDX-1 gene was transfected into hADMSCs by adenovirus. Cell differentiation and insulin secretion were identified and detected by dithizone staining and ELISA, respectively. Twenty male Sprague-Dawley rats were randomly divided into control group (n=4), diabetes group (n=8) and transplantation group (n=8). Rats in the latter two groups were subjected to making diabetic models by 65 mg/kg streptozotocin injection. Afterwards, rats in the transplantation group were given PDX-1 transfected ADMSCs via the tail vein.RESULTS AND CONCLUSION:At 15 days after transfection, the number of insulin positive cells and insulin secretion were both increased significantly (P < 0.05). Fasting glucose levels in the transplantation group decreased significantly (P < 0.05), while the body weight increased significantly (P < 0.05). In the diabetic group, the fasting glucose level still maintained at a high level, and the body weight of rats was significantly decreased. These results implicated that PDX-1 gene could induce hADMSCs differentiating into functional islet-like cells. PDX-1 transfected ADMSCs transplantation is effective in treating diabetic rats, but the mechanism needs further study.%背景:近年研究发现脂肪间充质干细胞不仅具有多向分化潜能,在血糖平衡及激素产生方面也具有重要作用.目的:观察PDX-1基因转染脂肪间充质干细胞向胰岛样细胞的分化能力及移植后对糖尿病大鼠的治疗效果.方法:采用腺病毒转染方法将PDX-1基因转入人脂肪间充质干细胞,双硫腙染色鉴定细胞分化情况,ELISA法检测细胞胰岛素分泌水平.从20只雄性SD大鼠中随机取4只作为对照组,注射生理盐水,其余16只按65 mg/kg的剂量注射链脲霉素建立糖尿病模型,再随机等分为移植组和糖尿病组,移植组大鼠尾静脉注射PDX-1基因转染脂肪间充质干细胞.结果与结论:①转染后15 d,转染组胰岛素阳性细胞数量、胰岛素分泌量均高于未转染组(P<0.05);②移植组大鼠空腹血糖水平显著下降(P<0.05),体质量明显增加(P<0.05),而糖尿病大鼠空腹血糖维持在较高水平,且体质量显著下降;③结果提示,导入PDX-1基因对人脂肪间充质干细胞分化为胰岛样细胞具有促进作用,PDX-1转染脂肪间充质干细胞移植能有效治疗大鼠糖尿病,但具体机制尚待进一步研究.