2012年9月26日 讯 /生物谷BIOON/ --在研究移植的胰岛细胞如何能够分化和成熟为产生胰岛素的胰腺细胞过程中，来自日本名古屋大学的一个研究小组发现利用一种被称作仙台病毒(Sendai virus, SeV)的小鼠流感病毒作为载体，能够将一组特异性的转录因子转导进小鼠胰腺干细胞(mouse pancreatic stem cells, mPSCs)。相关研究结果于近期刊登Cell Medicine期刊上，可以在线免费下载。
论文共同作者Hiroshi Yukawa说，“糖尿病是最为严重性和流行性代谢疾病之一。胰岛细胞移植已被证明是有效的，但是这种策略需要足够的捐赠器官。”
鉴于捐赠器官的短缺，研究人员利用小鼠病毒SeV将不同组合的转录因子导入胰腺干细胞来研究了能够影响胰腺干细胞增殖和分化为产生胰岛素的细胞的转录因子，从而能够增加用于移植的功能性胰岛细胞的数量。
研究人员说，SeV病毒载体要优于常规性的病毒载体，这是因为“它们(复制时)并不经历DNA阶段”，而且能够无毒地导入外源基因到多种细胞类型中。
对胰腺干细胞分化为产生胰岛素的细胞带来最大影响的转录因子组合是Pdx-1(Pancreatic and duodenal homeobox 1, 胰十二指肠同源盒基因-1)、NeuroD(neurogenic differentiation, 神经源性分化因子)和MafA(musculoaponeurotic fibrosarcoma oncogene A, 肌腱膜纤维肉瘤癌基因A)。研究人员作出结论，“我们的数据提示着利用SeV病毒载体导入转录因子能够促进小鼠胰腺干细胞分化为产生胰岛素的细胞，从而有可能利用转导的胰腺干细胞再生胰岛β细胞。” (生物谷Bioon.com)
doi: 10.3727/215517912X639487
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Differentiation of Mouse Pancreatic Stem Cells Into Insulin-Producing Cells by Recombinant Sendai Virus-Mediated Gene Transfer Technology
Yukawa, Hiroshi; Noguchi, Hirofumi; Oishi, Koichi; Miyamoto, Yoshitaka; Inoue, Makoto; Hasegawa, Mamoru; Hayashi, Shuji; Baba, Yoshinobu
Islet transplantation, including β-cells, has proven to be effective for diabetes in many recent studies; however, this treatment strategy requires sufficient organ donors. One attractive approach for the generation of β-cells is to utilize the expansion and differentiation of cells from pancreatic stem cells (PSCs), which are closely associated to the β-cells lineage. In this study, we investigated whether important transcription factors (Pdx-1, Ngn3, NeuroD, and MafA) in islet cells could be efficiently transduced into mouse PSCs (mPSCs) using Sendai virus (SeV) vectors and found that the transduced cells were differentiated into insulin-producing pancreatic β-cells. The mPSCs transduced with single transcription factors using SeV vectors could not express the insulin-2 mRNA. When combinations of two transcription factors were transduced using the SeV vectors, including combinations of Pdx-1 + NeuroD, Pdx-1 + MafA, and NeuroD + MafA, the expression of insulin-2 mRNA was low but could be detected. When combinations of three or more transcription factors were transduced using SeV vectors, the expression of insulin-2 mRNA could be detected. In particular, the transduction of the combination of PDX-1, NeuroD, and MafA produced the most effective for the expression of insulin-2 mRNA out of all of the different combinations examined. These data suggest that the transduction of transcription factors using SeV vectors facilitates mPSC differentiation into insulin-producing cells and showed the possibility of regenerating β-cells by using transduced PSCs.
