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首页> 外文期刊>Experimental diabetes research >Combined Transfection of the Three Transcriptional Factors, PDX-1, NeuroD1, and MafA, Causes Differentiation of Bone Marrow Mesenchymal Stem Cells into Insulin-Producing Cells
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Combined Transfection of the Three Transcriptional Factors, PDX-1, NeuroD1, and MafA, Causes Differentiation of Bone Marrow Mesenchymal Stem Cells into Insulin-Producing Cells

机译：三种转录因子PDX-1，NeuroD1和MafA的联合转染可导致骨髓间充质干细胞向胰岛素产生细胞的分化

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Aims. The goal of cell transcription for treatment of diabetes is to generate surrogateβ-cells from an appropriate cell line. However, the induced replacement cells have showed less physiological function in producing insulin compared with normalβ-cells.Methods. 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.Results. 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.Conclusions. These findings suggest major implications for cell replacement strategies in generation of surrogateβ-cells for the treatment of diabetes.
机译：目的细胞转录治疗糖尿病的目的是从合适的细胞系中产生替代β细胞。然而，与正常的β细胞相比，诱导的置换细胞在产生胰岛素方面显示出较少的生理功能。在这里，我们报告从骨髓鼠间充质干细胞（BM-mMSCs）诱导胰岛素生产细胞（IPCs）的程序。当PDX-1（胰腺和十二指肠同源盒-1），NeuroD1（神经分化-1）和MafA（V-maf肌腱膜纤维肉瘤癌基因同源物A）组合使用时，这些BM-mMSCs可能分化为产生胰岛素的细胞。基因被转染入它们并在这些细胞中表达。在已经转染并表达了这三个基因的mMSC中诱导了胰岛素的生物合成和分泌。已经被这三个基因一起转染的mMSC中的诱导胰岛素的量显着高于仅被这三个基因中的一个或两个转染的那些mMSC。将转染的细胞移植到患有链脲佐菌素诱导的糖尿病的小鼠体内可导致胰岛素表达和葡萄糖激发的逆转。这些发现暗示了用于治疗糖尿病的替代β-细胞的产生对细胞替代策略的重要意义。

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