糖尿病犬经肝动脉肝内移植微囊化猪胰岛细胞的安全性和有效性

目的评估移植于I型糖尿病犬肝脏中的微囊化新生猪胰岛细胞(NPI)的生物相容性、免疫学特性及生理学特性。方法I型糖尿病犬分为A、B两组,每组15只,A组每只犬分别经肝动脉灌注微囊化新生猪胰岛细胞40～60万个,B组每只犬分别经肝动脉灌注未微囊化新生猪胰岛细胞40～60万个,两组动物移植后均不使用免疫抑制治疗。移植前后分别测量移植受体的肝脏功能及淋巴细胞CD4 /CD8 比值。移植6个月后所有移植受体的肝脏均进行病理学检查。结果移植后A组外源性胰岛素用量从移植前的22 u逐渐降至5 u,B组所需外源性胰岛素从移植前的24 u下降至10 u。移植后2～3周B组胰岛素用量恢复到移植前的水平,而A组的部分动物的胰岛素剂量继续减至8 u。B组受体移植后血的CD4 较移植前升高,而A组的CD4 和CD8 细胞移植后无明显变化。移植后所有受体的肝功能及组织结构未见异常。结论微囊化的新生猪胰岛细胞在受体犬的肝脏中有很好的生物相容性。微囊可以延长移植物的存活,且异种移植微囊化的新生猪胰岛细胞能够纠正糖尿病犬的高血糖状态。

The safety and availability of xenotransplantated encapsulized newborn porcine islets into the diabetic dog's liver via hepatic artery

Objective To evaluate the biocompatibility,immunology and physiologic features of encapsulated Newborn Porcine Islets(NPI) in the liver of the recipient dogs with type I diabetes.Methods Type I diabetic dogs were perfused with 400 000-600 000 encapsulated NPI(group A,n = 15)or unencapsulated NPI(group B,n = 15)through the hepatic artery without immunosuppressive treatment.Liver function and CD4/CD8 in the recipients were measured before and after the transplantation.The livers from all NPI recipient dogs were analyzed by histopathology 6 months after transplantation(Tx).Results Insulin dose administrated to group A was reduced gradually within one week after Tx,from 22 u before Tx to 5 u after Tx,exogenous insulin required for group B was decreased from 24 u to 10 u.However,2 to 3 weeks after Tx,the insulin dose given to group B returned to the original level before Tx.In contrast,the amount of insulin administrated to group A was continually reduced to 8 u.Moreover,CD4 cells in the blood of group B recipients were higher than that before Tx,whereas no significant alteration of CD4 cells and CD8 cells in the blood of group A after Tx.All NPI recipient dogs demonstrated a normal function and structure of the liver after Tx.Conclusion Microcapsulated NPI has a good biocompatibility in recipients livers providing prolong-ation of xenograft survival,and correcting the hyperglycemia of diabetic canines.(J Intervent Radiol,2006,15: 607-610)