BACKGROUND:Pancreas or islet cel transplantation and stem cel transplantation bring hope to cure diabetes, but pancreas or islet transplantation appears to have a lack of donors as wel as immune rejection problems, limiting their clinical development. Therefore, stem cel transplantation therapy has become the current hotspot. OBJECTIVE:To study the therapeutic effects of huaman telomerase reverse transcriptase (hTERT)-modified bone marrow mesenchymal stem cel s transplantation on diabetes mel itus in SD rats. METHODS:Bone marrow mesenchymal stem cel s were transfected with PLXSN carrying hTERT. Thirty-six male SD rats were randomly divided into control group (n=6), stem cel group (n=10), hTERT transfection group (n=10), diabetes mel itus group (n=10). Except the control group, the rats were injected with stretozotocin (45 mg/kg) to make diabetes mel itus models. After modeling, rats in the stem cel group and hTERT transfection group were respectively intravenously injected with 1 mL of bone marrow mesenchymal stem cel s (1.5×1010/L) and 1 mL of hTERT-modified bone marrow mesenchymal stem cel s (1.5×1010/L). RESULTS AND CONCLUSION:At 24 hours after modeling, the fasting blood-glucose level was significantly increased in the diabetes mel itus group, which was higher than the normal value (6.7 mmol/L). At 15 days after cel transplantation, the fasting blood-glucose levels were signficiantly decreased in the stem cel group and hTERT transfection group as compared with the diabetes mel itus group (P<0.05), but the body mass of rats was increased in these two group (P<0.05), especial y in the hTERT transfection group. At 45 days after cel transplantation, the fasting blood-glucose level and body mass in the stem cel group and hTERT transfection group were close to those in the control group (P>0.05), and moreover, the hTERT group had better outcomes than the stem cel group. Meanwhile, in the diabetes mel itus group, the fasting blood-glucose level was stil at a higher level, and the body mass decreased continously. These findings suggest that hTERT-modified bone marrow mesenchymal stem cel transplantation is effective for treatment of diabetes mel itus in rats.%背景：胰腺或胰岛细胞移植以及干细胞移植治疗为根治糖尿病带来了希望，但是胰腺或胰岛移植会出现供者缺乏和免疫排异反应问题而限制了其在临床的发展，因此干细胞移植治疗成为目前研究的热点。 目的：观察人端粒酶反转录酶基因修饰的骨髓间充质干细胞移植对SD大鼠糖尿病的治疗效果。 方法：以反转录病毒PLXSN为载体介导人端粒酶反转录酶基因转染骨髓间充质干细胞。从36只雄性SD大鼠中随机取6只作为对照组，注射生理盐水，其余30只注射链脲霉素(按45 mg/kg)建立糖尿病模型后，随机等分为干细胞组、人端粒酶反转录酶基因转染干细胞组和糖尿病组。造模后干细胞组、人端粒酶反转录酶基因转染干细胞组大鼠通过尾静脉注入1 mL骨髓间充质干细胞(1.5×1010 L-1)和1 mL人端粒酶反转录酶基因转染骨髓间充质干细胞(1.5×1010 L-1)。 结果与结论：注射链脲霉素24 h 后，与对照组相比，糖尿病组大鼠空腹血糖明显增加，且高于正常值(6.7 mmol/L)；移植后15 d，与糖尿病组相比，干细胞组、人端粒酶反转录酶基因转染干细胞组大鼠空腹血糖水平显著下降(P <0.05)，体质量显著增加(P <0.05)，人端粒酶反转录酶基因转染干细胞组较干细胞组更为明显；移植后45 d，干细胞组、人端粒酶反转录酶基因转染干细胞组大鼠空腹血糖水平与体质量接近对照组(P>0.05)，人端粒酶反转录酶基因转染干细胞组优于干细胞组，而糖尿病组大鼠空腹血糖维持较高水平，且体质量持续下降。上述结果提示人端粒酶反转录酶基因转染的骨髓间充质干细胞能有效治疗大鼠糖尿病。
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