Department of Clinical Pathology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.
Tissue Cell. 2011 Apr;43(2):75-82. doi: 10.1016/j.tice.2010.12.002. Epub 2011 Jan 20.
Cellular replacement therapy is a potential therapeutic strategy for diabetes. In this study, we investigated the effect of transplantation of induced mouse embryonic stem cells (mESCs) into endoderm and early hepatocyte-like cells in streptozotocin (STZ)-diabetic mice. After embryoid body (EB) formation from mESC, the EBs were cultured in the presence of dexamethasone (DEX) and insulin for 4 days then was added acidic fibroblast growth factor (aFGF), hepatocyte growth factor (HGF) and oncostatin M (OSM) for 10 days, respectively. Blood glucose levels, intraperitoneal glucose tolerance (IGT) test and islet histology were assessed. The result revealed that transplantation of induced mESCs into early hepatocyte-like cells could repair pancreatic islets of control group. Blood glucose levels and intraperitoneal glucose tolerance test were significantly improved in test group compared to control group. Furthermore, there was significant increase in the number of islets in test group compared to control group. The findings declare that induced mESCs into endoderm and early hepatocyte-like cells, are appropriate candidate for regenerative therapy of pancreatic islets in type I diabetes.
细胞替代疗法是糖尿病的一种潜在治疗策略。在这项研究中,我们研究了将诱导的小鼠胚胎干细胞(mESC)移植到链脲佐菌素(STZ)-糖尿病小鼠的内胚层和早期肝样细胞中的效果。从小鼠胚胎干细胞形成胚状体(EB)后,将 EB 在含有地塞米松(DEX)和胰岛素的条件下培养 4 天,然后分别添加酸性成纤维细胞生长因子(aFGF)、肝细胞生长因子(HGF)和抑瘤素 M(OSM)培养 10 天。评估血糖水平、腹腔内葡萄糖耐量(IGT)试验和胰岛组织学。结果表明,将诱导的 mESC 移植到早期肝样细胞中可以修复对照组的胰岛。与对照组相比,试验组的血糖水平和腹腔内葡萄糖耐量试验显著改善。此外,与对照组相比,试验组胰岛数量明显增加。这些发现表明,将诱导的 mESC 分化为内胚层和早期肝样细胞,是 1 型糖尿病胰岛再生治疗的合适候选物。