胎肝间充质干细胞治疗实验性糖尿病小鼠的研究

Treatment of experimental diabetes mice using mesenchymal stem cells from fetal liver

目的：研究胎肝间充质干细胞向胰岛β样细胞分化和治疗1型糖尿病的可行性。方法：用贴壁筛选法从正常C57BL／6j胎鼠（孕11．5～15．5d）肝脏中分离出胎肝间充质干细胞，用高浓度葡萄糖、碱性成纤维细胞生长因子（bFGF）和尼克酰胺体外诱导胎肝间充质干细胞向胰岛B样细胞分化；制作1型糖尿病小鼠模型，并将诱导后的细胞移植到1型糖尿病小鼠肾被膜下，连续6周观察血糖变化；用组织学分析移植细胞体内的发育。结果：胎肝间充质干细胞来源的胰岛β样细胞移植到糖尿病小鼠肾被膜下后，具有一定的降低血糖的作用，经过6周以后，接近正常水平；取出移植物，小鼠高血糖重新出现，并很快死亡；移植物作免疫组织化学染色，可以观察到肾被膜下区含有大量胰岛素阳性细胞。结论：胎肝间充质干细胞有望成为1型糖尿病胰岛移植的种子细胞。

Aim：To study the possibility of curing experimental murine type 1 diabetes with the insulin producing cells induced by mesenchymal stem cells （MSCs） from fetal liver. Methods： MSCs were isolated from C57BL/6J mouse fetal liver （E11.5-E15.5） by adhesive screening method and induced by high glucose, bFGF （basic fibroblast growth factor）, nicotamine in vitro culture. Diabetes mice were made by STZ. We transplanted the induced cells into STZ-diabetes mice and monitored the blood glucose in 6 weeks. The grafts were taken out from the mouse body and the assay of tissue were done with immunochemistry methods. Results： After grafted with insulin producing cells, glucose level of ST-Z-diabetes mice reached normal level week 6 end. The grafts were taken out from the STZ-diabetes mouse body, which died in a few days. The immunochemistry assay of grafts showed that there is a lot of insulin in graft cells. Conclusion：There is a possibility that MSCs derived from fetal liver will be used to treat type 1 diabetes.