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目的探讨类β细胞自体肝内移植对糖尿病Beagle犬的长期疗效及安全性。方法通过逆转录病毒载体pMSCV将外源性胰岛素基因和EGFP基因转导入Beagle犬骨髓间充质干细胞(BMSCs),制备类β细胞。然后运用肝动脉介入技术,将类β细胞自体移植入糖尿病Beagle犬肝内,通过监测比较糖尿病Beagle犬移植前后各项生理指标,评价其是否具有长期稳定的治疗效果,同时进行肝脏生理功能及病理组织形态学检测,并对其生物安全性进行验证。结果自体移植类β细胞对糖尿病Beagle犬血糖、体质量、胰岛素水平均有明显改善(均P<0.01),且疗效持续80周以上;Beagle的肝功能正常(P>0.05),移植部位的肝脏未发现肿瘤形成,具有可靠的生物安全性。结论自体肝内移植类β细胞对Beagle犬糖尿病有长期疗效且具有相对可靠的生物安全性。
Objective To investigate the long-term efficacy and safety of β-cell autologous intra-liver transplantation in diabetic Beagle dogs. Methods The exogenous insulin gene and EGFP gene were transduced into Beagle dog bone marrow mesenchymal stem cells (BMSCs) by retroviral vector pMSCV to prepare β-cell. Then the hepatic artery interventional technique was used to autologously transplanted β-cells into the liver of diabetic Beagle dogs. The physiological indexes before and after the transplantation of diabetic Beagle dogs were compared to evaluate whether they have long-term and stable therapeutic effects. Meanwhile, the physiological function and pathology of liver Histomorphological test, and verify its biosafety. Results The blood glucose, body weight and insulin level in diabetic Beagle dogs were significantly improved (all P <0.01), and the curative effect lasted more than 80 weeks. Beagle’s liver function was normal (P> 0.05) No tumor formation was found, with reliable biosafety. Conclusion Autologous intrahepatic transplantation of β-cells has a long-term effect on Beagle dogs with diabetes and has relatively reliable biosafety.