在一項(xiàng)新研究中,，來自美國沙克生物研究所的研究人員發(fā)現(xiàn)一種新方法：利用一種被稱作轉(zhuǎn)錄因子的蛋白來講臍帶血細(xì)胞轉(zhuǎn)化為神經(jīng)元樣細(xì)胞(neuron-like cell)。這種神經(jīng)元樣細(xì)胞有可能被用來治療一系列神經(jīng)疾病,，包括中風(fēng),、創(chuàng)傷性腦損傷和脊髓損傷,。
研究人員證實(shí)這些來自中胚層(mesoderm)的臍帶血細(xì)胞的能夠轉(zhuǎn)換到外胚層細(xì)胞，而正是外胚層細(xì)胞產(chǎn)生腦細(xì)胞,、脊髓細(xì)胞和神經(jīng)細(xì)胞,。論文通訊作者、沙克生物研究所基因表達(dá)實(shí)驗(yàn)室教授Juan Carlos Izpisua Belmonte說,，“這項(xiàng)研究是第一次證實(shí)通過誘導(dǎo)表達(dá)單個(gè)轉(zhuǎn)錄因子就能夠?qū)⒓兊娜四殠а?xì)胞直接轉(zhuǎn)化為神經(jīng)元譜系的細(xì)胞,。”相關(guān)研究結(jié)果于2012年7月16日發(fā)表在PNAS上。
研究人員利用一種逆轉(zhuǎn)錄病毒來導(dǎo)入一種轉(zhuǎn)錄因子Sox2到臍帶血細(xì)胞中,，其中Sox2作為神經(jīng)元發(fā)育的一種開關(guān)而發(fā)揮作用,。在實(shí)驗(yàn)室中培養(yǎng)之后，他們發(fā)現(xiàn)表達(dá)神經(jīng)元標(biāo)記物的細(xì)胞集落,。利用多種測試方法,，他們確定這些被稱作誘導(dǎo)性神經(jīng)元樣細(xì)胞(induced neuronal-like cell, iNC)的新細(xì)胞能夠傳遞電脈沖，從而表明這些細(xì)胞是成熟的功能性神經(jīng)元,。此外,，他們將導(dǎo)入Sox2的臍帶血細(xì)胞移植到小鼠大腦之中,，發(fā)現(xiàn)它們整合到現(xiàn)存的小鼠神經(jīng)元網(wǎng)絡(luò)之中，并且能夠像成熟的功能性神經(jīng)元那樣傳遞電信號(hào),。
論文共同第一作者M(jìn)o Li說,，“我們也證實(shí)這些臍帶血來源的神經(jīng)元能夠在一定條件下增殖，并且在實(shí)驗(yàn)室中和小鼠大腦內(nèi)仍然保持分化為更多的成熟神經(jīng)元的能力,。盡管我們開發(fā)的這些細(xì)胞不能只分化為諸如運(yùn)動(dòng)哦你神經(jīng)元或中腦神經(jīng)元之類的特定細(xì)胞系,，但是我們希望在未來產(chǎn)生臨床上比較重要的神經(jīng)元亞型。”
臍帶血細(xì)胞要比其他類型的干細(xì)胞有很多優(yōu)勢,。首先,，它們不是胚胎干細(xì)胞，因而不會(huì)引起爭議,。它們也比來自諸如骨髓之類來源的成體干細(xì)胞更具可塑性或靈活性,，這就使得它們更加容易轉(zhuǎn)化為特定的細(xì)胞系。收集臍帶血細(xì)胞比較安全,，不會(huì)產(chǎn)生疼痛,，而且對(duì)供者也不會(huì)產(chǎn)生風(fēng)險(xiǎn)，因此它們能夠被儲(chǔ)存在血庫中以便未來使用,。(生物谷：Bioon.com)
本文編譯自Neurons derived from cord blood cells may represent new therapeutic option
doi: 10.1073/pnas.1209523109
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PMID:
Cord blood-derived neuronal cells by ectopic expression of Sox2 and c-Myc
Alessandra Giorgettia,1,2, Maria C. N. Marchettob,1, Mo Lic,1, Diana Yub, Raffaella Fazzinaa, Yangling Mub, Antonio Adamoa, Ida Paramonova, Julio Castaño Cardosoa, Montserrat Barragan Monasterioa, Cedric Bardyb, Riccardo Cassiani-Ingonia, Guang-Hui Liuc, Fred H. Gageb,3, and Juan Carlos Izpisua Belmonte
The finding that certain somatic cells can be directly converted into cells of other lineages by the delivery of specific sets of transcription factors paves the way to novel therapeutic applications. Here we show that human cord blood (CB) CD133+ cells lose their hematopoietic signature and are converted into CB-induced neuronal-like cells (CB-iNCs) by the ectopic expression of the transcription factor Sox2, a process that is further augmented by the combination of Sox2 and c-Myc. Gene-expression analysis, immunophenotyping, and electrophysiological analysis show that CB-iNCs acquire a distinct neuronal phenotype characterized by the expression of multiple neuronal markers. CB-iNCs show the ability to fire action potentials after in vitro maturation as well as after in vivo transplantation into the mouse hippocampus. This system highlights the potential of CB cells and offers an alternative means to the study of cellular plasticity, possibly in the context of drug screening research and of future cell-replacement therapies.
