1月30日,，《美國(guó)國(guó)家科學(xué)院院刊》上的一項(xiàng)研究表明,，美國(guó)科學(xué)家成功繞過(guò)干細(xì)胞階段，將老鼠的皮膚細(xì)胞直接轉(zhuǎn)化成神經(jīng)前體細(xì)胞,，得到的細(xì)胞能發(fā)育成三種腦細(xì)胞,，而且能在實(shí)驗(yàn)室里大量培育。新方法為受損神經(jīng)細(xì)胞再生提供了一條新途徑,，在醫(yī)療領(lǐng)域擁有巨大的應(yīng)用潛力,。不過(guò)，他們也指出,，這項(xiàng)技術(shù)用于人體之前還需要進(jìn)行很多研究,。
大腦細(xì)胞和皮膚細(xì)胞含有同樣的遺傳信息，然而,，在“轉(zhuǎn)錄因子”的控制下,，這兩種細(xì)胞內(nèi)的遺傳代碼被不同地解讀。
在實(shí)驗(yàn)中,，斯坦福醫(yī)學(xué)院的馬里厄斯·韋尼希斯領(lǐng)導(dǎo)的科研團(tuán)隊(duì)使用一個(gè)病毒激活老鼠皮膚細(xì)胞中的三種轉(zhuǎn)錄因子,，這三種轉(zhuǎn)錄因子在神經(jīng)前體細(xì)胞中具有很高的濃度。三周后,，約十分之一的皮膚細(xì)胞變成了神經(jīng)前體細(xì)胞,，得到的神經(jīng)前體細(xì)胞能發(fā)育成三種大腦細(xì)胞：神經(jīng)細(xì)胞、星形膠質(zhì)細(xì)胞和少突（神經(jīng)）膠質(zhì)細(xì)胞,。而且,，這些神經(jīng)前體細(xì)胞還具有一個(gè)優(yōu)勢(shì)，那就是：一旦它們被制造出來(lái),，就能在實(shí)驗(yàn)室內(nèi)大量培育,，這一點(diǎn)對(duì)得到的細(xì)胞用于治療非常關(guān)鍵。
韋尼希斯表示：“我們已經(jīng)證明,，這些細(xì)胞能整合進(jìn)老鼠的大腦中并產(chǎn)生一個(gè)對(duì)神經(jīng)細(xì)胞的電信號(hào)傳導(dǎo)非常重要的蛋白質(zhì),。我們對(duì)這些細(xì)胞的應(yīng)用前景深感興奮。”
科學(xué)家們表示，他們的最新研究繞過(guò)了中間階段——干細(xì)胞階段,。干細(xì)胞療法面臨一個(gè)巨大問(wèn)題：從何處得到干細(xì)胞,？使用胚胎干細(xì)胞存在倫理爭(zhēng)議；另外,，當(dāng)干細(xì)胞組織與病人的身體組織不匹配時(shí),，病人還需服用免疫抑制劑藥物。替代方法之一是使用皮膚細(xì)胞并對(duì)其進(jìn)行編程,，讓其成為“誘導(dǎo)”干細(xì)胞,。這些皮膚細(xì)胞能從病人自己的身體中提取，也能變成病人需要的任何類(lèi)型細(xì)胞,，但這個(gè)過(guò)程會(huì)導(dǎo)致誘發(fā)癌癥的基因被激活,。最新研究繞過(guò)“誘導(dǎo)”干細(xì)胞階段，將人體皮膚細(xì)胞直接轉(zhuǎn)化為特定的細(xì)胞類(lèi)型,。
加州舊金山格萊斯頓心血管疾病研究所的發(fā)育生物學(xué)家迪帕卡·斯利維司塔瓦已成功地將細(xì)胞轉(zhuǎn)化為心肌細(xì)胞,，他說(shuō)：“這項(xiàng)研究為我們使用細(xì)胞讓受損的神經(jīng)細(xì)胞再生提供了一條新途徑。”不過(guò),，韋尼希斯也指出，在最新技術(shù)用于人體前,，還需要進(jìn)行很多測(cè)試工作以對(duì)其安全性和效率進(jìn)行評(píng)估,。（生物谷 Bioon.com）
doi:10.1073/pnas.1121003109
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Direct conversion of mouse fibroblasts to self-renewing, tripotent neural precursor cells
Ernesto Lujan, Soham Chanda, Henrik Ahlenius, Thomas C. Südhof, and Marius Wernig
We recently showed that defined sets of transcription factors are sufficient to convert mouse and human fibroblasts directly into cells resembling functional neurons, referred to as “induced neuronal” (iN) cells. For some applications however, it would be desirable to convert fibroblasts into proliferative neural precursor cells (NPCs) instead of neurons. We hypothesized that NPC-like cells may be induced using the same principal approach used for generating iN cells. Toward this goal, we infected mouse embryonic fibroblasts derived from Sox2-EGFP mice with a set of 11 transcription factors highly expressed in NPCs. Twenty-four days after transgene induction, Sox2-EGFP+ colonies emerged that expressed NPC-specific genes and differentiated into neuronal and astrocytic cells. Using stepwise elimination, we found that Sox2 and FoxG1 are capable of generating clonal self-renewing, bipotent induced NPCs that gave rise to astrocytes and functional neurons. When we added the Pou and Homeobox domain-containing transcription factor Brn2 to Sox2 and FoxG1, we were able to induce tripotent NPCs that could be differentiated not only into neurons and astrocytes but also into oligodendrocytes. The transcription factors FoxG1 and Brn2 alone also were capable of inducing NPC-like cells; however, these cells generated less mature neurons, although they did produce astrocytes and even oligodendrocytes capable of integration into dysmyelinated Shiverer brain. Our data demonstrate that direct lineage reprogramming using target cell-type–specific transcription factors can be used to induce NPC-like cells that potentially could be used for autologous cell transplantation-based therapies in the brain or spinal cord.
