自体骨髓间充质干细胞经动脉介入移植治疗犬糖尿病

背景:目前多数研究倾向于将骨髓间充质干细胞经静脉移植等方法移植入糖尿病动物模型体内,而缺少将骨髓间充质干细胞经动脉介入移植入糖尿病动物模型胰腺内的相关研究。目的:用自体骨髓间充质干细胞经动脉介入移植入糖尿病犬胰腺内,观察骨髓间充质干细胞的分布、分化、对糖尿病的治疗效果及安全性。方法:将30只家犬随机分为骨髓间充质干细胞组(治疗组,n=13),糖尿病模型对照组(模型组,n=10)和对照组(n=7)。治疗组及模型组通过静脉注射四氧嘧啶建立糖尿病模型。造模后,治疗组进行胰岛素治疗,同时进行自体骨髓间充质干细胞的动脉介入移植。模型组仅接受胰岛素治疗,对照组则不接受任何治疗。结果与结论:与模型组比较,治疗组于移植后第12周的胰岛素用量明显减少(P<0.05),血清C-肽水平明显升高(P<0.05)。治疗组于移植后第4周及12周的组织病理切片显示,心脏、肝脏、脾脏、肺脏、肾脏的组织结构清晰,均未发生坏死、纤维化,与模型组及对照组比较,移植后各器官组织形态无明显异常改变。移植后第4周,骨髓间充质干细胞主要分布在胰腺及肾脏内,免疫荧光发现胰腺内存在CM-DiI和胰岛素共表达细胞。表明将骨髓间充质干细胞经动脉介入移植入糖尿病犬胰腺内来治疗糖尿病的方法,是安全有效的。

Intra-arterial transplantation of autologous bone marrow mesenchymal stem cells for treatment of diabetes in dogs

BACKGROUND: At present, most researchers focus on intravenous transplantation of bone marrow mesenchymal stem cells (BMSCs) into diabetic animal models. There are few studies that describe transplantation of BMSCs into the pancreas of diabetic animal models via arterial intervention. OBJECTIVE: To investigate the distribution and differentiation of autologous BMSCs transplanted into the pancreas of a dog model of diabetes via the arterial intervention as well as the therapeutic effects and safety. METHODS: 30 dogs were randomly divided into BMSCs group (treatment group, n=13), diabetic model control group (model control group, n=10) and normal control group (n=7). Dogs in treatment group and model control group were intravenously injected with alloxan to establish diabetes models. After model establishment, treatment group received insulin therapy and autologous transplantation of BMSCs via arterial intervention. Model control group only received insulin therapy, and normal control group did not receive any treatment. RESULTS AND CONCLUSION: Compared with the model control group, insulin dosage significantly decreased and serum C-peptide level significantly increased (P < 0.05) in the treatment group (P < 0.05) at 12 weeks after transplantation. At 4 and 12 weeks after transplantation, the frozen sections of treatment group showed that the heart, liver, spleen, lung and kidney had clear structure, without necrosis and fibrosis. Compared with model control group and normal control group, the morphological structure of each organ had no obvious abnormal change after transplantation in the treatment group. At 4 weeks after transplantation, BMSCs mainly distributed in the pancreas and kidney, and CM-DiI and insulin double-positive cells were in the pancreas as detected by immunofluorescence staining. The results suggest that the method of transplantation of autologous BMSCs via arterial intervention for treatment of diabetic dogs is safe and effective.