2012年9月26日 訊 /生物谷BIOON/ --在研究移植的胰島細(xì)胞如何能夠分化和成熟為產(chǎn)生胰島素的胰腺細(xì)胞過程中,，來自日本名古屋大學(xué)的一個研究小組發(fā)現(xiàn)利用一種被稱作仙臺病毒(Sendai virus, SeV)的小鼠流感病毒作為載體，能夠?qū)⒁唤M特異性的轉(zhuǎn)錄因子轉(zhuǎn)導(dǎo)進(jìn)小鼠胰腺干細(xì)胞(mouse pancreatic stem cells, mPSCs),。相關(guān)研究結(jié)果于近期刊登Cell Medicine期刊上,，可以在線免費下載,。
論文共同作者Hiroshi Yukawa說，“糖尿病是最為嚴(yán)重性和流行性代謝疾病之一,。胰島細(xì)胞移植已被證明是有效的,，但是這種策略需要足夠的捐贈器官,。”
鑒于捐贈器官的短缺，研究人員利用小鼠病毒SeV將不同組合的轉(zhuǎn)錄因子導(dǎo)入胰腺干細(xì)胞來研究了能夠影響胰腺干細(xì)胞增殖和分化為產(chǎn)生胰島素的細(xì)胞的轉(zhuǎn)錄因子,，從而能夠增加用于移植的功能性胰島細(xì)胞的數(shù)量,。
研究人員說，SeV病毒載體要優(yōu)于常規(guī)性的病毒載體,，這是因為“它們(復(fù)制時)并不經(jīng)歷DNA階段”,，而且能夠無毒地導(dǎo)入外源基因到多種細(xì)胞類型中。
對胰腺干細(xì)胞分化為產(chǎn)生胰島素的細(xì)胞帶來最大影響的轉(zhuǎn)錄因子組合是Pdx-1(Pancreatic and duodenal homeobox 1, 胰十二指腸同源盒基因-1),、NeuroD(neurogenic differentiation, 神經(jīng)源性分化因子)和MafA(musculoaponeurotic fibrosarcoma oncogene A, 肌腱膜纖維肉瘤癌基因A),。研究人員作出結(jié)論，“我們的數(shù)據(jù)提示著利用SeV病毒載體導(dǎo)入轉(zhuǎn)錄因子能夠促進(jìn)小鼠胰腺干細(xì)胞分化為產(chǎn)生胰島素的細(xì)胞,，從而有可能利用轉(zhuǎn)導(dǎo)的胰腺干細(xì)胞再生胰島β細(xì)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.
