【摘要】：尋找具有多項(xiàng)分化潛能和自我更新能力的細(xì)胞是近年來(lái)再生醫(yī)學(xué)領(lǐng)域研究的重點(diǎn)課題,而人胚胎干細(xì)胞(human embryonic stem cell, hESC)是干細(xì)胞應(yīng)用最佳的備選材料。由于受到倫理學(xué)問(wèn)題和免疫性排斥等方面因素的影響,hESC在臨床上的應(yīng)用面臨巨大的障礙。尋找新的干細(xì)胞備選材料是目前國(guó)內(nèi)外干細(xì)胞研究領(lǐng)域相關(guān)專家共同關(guān)心的課題之一。人誘導(dǎo)多能分化干細(xì)胞(induced pluripotent stem cells, iPSC)技術(shù)的發(fā)現(xiàn)是近年來(lái)干細(xì)胞研究領(lǐng)域中一個(gè)里程碑式的突破。iPSC技術(shù)通過(guò)應(yīng)用逆轉(zhuǎn)錄病毒轉(zhuǎn)染系統(tǒng),在成體細(xì)胞中導(dǎo)入一個(gè)或幾個(gè)轉(zhuǎn)錄因子,從而使成體細(xì)胞重編程為具有多項(xiàng)分化潛能的iPSC�；诓煌z傳背景的人多能干細(xì)胞系的建立及其多向分化潛能研究可為iPSC的臨床應(yīng)用奠定理論基礎(chǔ)。 脊髓性肌萎縮癥(spinal muscular atrophy, SMA)包括一組常染色體隱性遺傳性神經(jīng)系統(tǒng)疾病,其中兒童型(Ⅰ-Ⅲ)是由其致病基因—運(yùn)動(dòng)神經(jīng)元生存基因(survival of motor neuron, SMN)—端粒側(cè)拷貝SMN1缺失引起,表現(xiàn)為脊髓前角細(xì)胞變性所致的肌無(wú)力和肌萎縮,并且本病至今無(wú)有效治療。iPSC技術(shù)的問(wèn)世及其高效的分化為神經(jīng)元亞型的能力為研究SMA等神經(jīng)遺傳性疾病提供了一種新的有利的工具。 成纖維細(xì)胞生長(zhǎng)因子(fibroblast growth factor, FGF)家族對(duì)于促進(jìn)細(xì)胞分裂增殖和血管生成起著非常重要的作用,近來(lái)有相關(guān)研究表明FGF能夠促進(jìn)人神經(jīng)的再生與修復(fù),而且最近有研究發(fā)現(xiàn)FGF信號(hào)在hESC神經(jīng)分化中起到積極的促進(jìn)作用。但是有關(guān)FGF信號(hào)通路在iPSC早期神經(jīng)分化中的作用至今仍未見報(bào)道。 我們采用逆轉(zhuǎn)錄病毒轉(zhuǎn)染系統(tǒng)和慢病毒轉(zhuǎn)染系統(tǒng)成功地建立了正常人來(lái)源(TZ1、YZ1)及SMA病人來(lái)源的iPSC細(xì)胞株(SMA-W1),經(jīng)相關(guān)檢測(cè)發(fā)現(xiàn)它們均具有跟hESC相似的多向分化潛能,同時(shí)我們還探討了FGF信號(hào)通路在iPSC早期神經(jīng)分化中的重要作用,并且發(fā)現(xiàn)小分子化合物(purmorphamine)能顯著提高iPSC向后腦及脊髓運(yùn)動(dòng)神經(jīng)元分化的效率。我們的研究工作有助于更加深入地了解iPSC神經(jīng)分化的誘導(dǎo)和調(diào)控,并且為iPSC在SMA治療中的應(yīng)用提供了理想的細(xì)胞模型和堅(jiān)實(shí)的實(shí)驗(yàn)基礎(chǔ)。
[Abstract]:In recent years, searching for cells with multiple differentiation potential and self-renewal ability has been a key topic in the field of regenerative medicine. Human embryonic stem cell (human embryonic stem cell, hESC) is the best candidate material for the application of stem cells. Due to the influence of ethical problems and immunological rejection, the clinical application of hESC is faced with great obstacles. To search for new stem cell materials is one of the topics concerned by relevant experts in stem cell research at home and abroad. The discovery of human induced pluripotent stem cell (induced pluripotent stem cells, iPSC) technology is a landmark breakthrough in stem cell research in recent years. IPSC technology has been used in retrovirus transfection systems. Introduction of one or more transcription factors into adult cells so that adult cells are reprogrammed as iPSC. with multiple differentiation potentials The establishment of human pluripotent stem cell lines based on different genetic backgrounds and their multidirectional differentiation potential can lay a theoretical foundation for the clinical application of iPSC. Spinal muscular atrophy (spinal muscular atrophy, SMA) includes a group of autosomal recessive nervous system diseases, in which the childhood type (鈪，

本文編號(hào)：2342035