Guo Qing-Song, Zhu Ming-Yan, Wang Lei, Fan Xiang-Jun, Lu Yu-Hua, Wang Zhi-Wei, Zhu Sha-Jun, Wang Yao, Huang Yan
Department of General Surgery, Affiliated Hospital of Nantong University, Nantong 226001, China.
Exp Diabetes Res. 2012;2012:672013. doi: 10.1155/2012/672013. Epub 2012 Jun 19.
The goal of cell transcription for treatment of diabetes is to generate surrogate β-cells from an appropriate cell line. However, the induced replacement cells have showed less physiological function in producing insulin compared with normal β-cells.
Here, we report a procedure for induction of insulin-producing cells (IPCs) from bone marrow murine mesenchymal stem cells (BM-mMSCs). These BM-mMSCs have the potential to differentiate into insulin-producing cells when a combination of PDX-1 (pancreatic and duodenal homeobox-1), NeuroD1 (neurogenic differentiation-1), and MafA (V-maf musculoaponeurotic fibrosarcoma oncogene homolog A) genes are transfected into them and expressed in these cells.
Insulin biosynthesis and secretion were induced in mMSCs into which these three genes have been transfected and expressed. The amount of induced insulin in the mMSCs which have been transfected with the three genes together is significantly higher than in those mMSCs that were only transfected with one or two of these three genes. Transplantation of the transfected cells into mice with streptozotocin-induced diabetes results in insulin expression and the reversal of the glucose challenge.
These findings suggest major implications for cell replacement strategies in generation of surrogate β-cells for the treatment of diabetes.
通过细胞转录治疗糖尿病的目标是从合适的细胞系中生成替代β细胞。然而，与正常β细胞相比，诱导产生的替代细胞在产生胰岛素方面表现出较低的生理功能。
在此，我们报告了一种从骨髓小鼠间充质干细胞（BM - mMSC）诱导产生胰岛素分泌细胞（IPC）的方法。当将胰腺十二指肠同源盒 - 1（PDX - 1）、神经源性分化因子 - 1（NeuroD1）和肌肉腱膜纤维肉瘤癌基因同源物A（MafA）这三种基因组合转染到这些BM - mMSC中并在细胞中表达时，它们具有分化为胰岛素分泌细胞的潜力。
在转染并表达了这三种基因的mMSC中诱导出了胰岛素的生物合成和分泌。同时转染了这三种基因的mMSC中诱导产生的胰岛素量显著高于仅转染其中一两种基因的mMSC。将转染后的细胞移植到链脲佐菌素诱导的糖尿病小鼠体内，可导致胰岛素表达并逆转葡萄糖应激。
这些发现表明在为治疗糖尿病生成替代β细胞的细胞替代策略方面具有重要意义。
