據(jù)英國(guó)《新科學(xué)家》雜志網(wǎng)站近日?qǐng)?bào)道,，兩個(gè)科研小組分別宣布，他們對(duì)老鼠皮膚細(xì)胞和人類皮膚細(xì)胞進(jìn)行基因重組,，將其變成了能制造多巴胺的特定神經(jīng)元,。未來，帕金森氏癥患者有望借助用自己的皮膚制成的神經(jīng)元來醫(yī)治自己的病癥,。
科學(xué)家們表示,，在帕金森氏癥患者大腦內(nèi),，多巴胺這種對(duì)人的活動(dòng)能力至關(guān)重要的神經(jīng)傳遞素已被消耗殆盡。目前,，帕金森氏癥患者多服用名為左旋多巴的藥物來重新調(diào)整大腦內(nèi)多巴胺的濃度,，但成功率因個(gè)體差異有高有低。而新研究表明,，通過將患者自身的皮膚細(xì)胞變?yōu)樯窠?jīng)元來制造多巴胺,，使之在大腦內(nèi)的濃度恢復(fù)至正常水平，可改善患者的運(yùn)動(dòng)能力,。
來自于意大利米蘭圣拉斐爾科研所的范尼亞·波切利和同事使用三個(gè)轉(zhuǎn)錄因子（同神經(jīng)元的發(fā)育有關(guān)的蛋白質(zhì)）,，對(duì)實(shí)驗(yàn)老鼠的皮膚細(xì)胞進(jìn)行了重組。同樣的三個(gè)轉(zhuǎn)錄因子也可將從人類胚胎,、健康成年人和帕金森氏癥患者體內(nèi)提取而來的皮膚細(xì)胞變成神經(jīng)元,。這種方法唯一的缺陷是，他們不得不先用攜帶了基因來制造轉(zhuǎn)錄因子的病毒來感染皮膚細(xì)胞,，盡管使用病毒并不會(huì)破壞DNA（脫氧核糖核酸）,，也不會(huì)引發(fā)癌癥。相關(guān)論文發(fā)表于《自然》（Nature）雜志,。
波切利表示,，他的團(tuán)隊(duì)正在測(cè)試，用實(shí)驗(yàn)鼠細(xì)胞以及人體細(xì)胞制成的神經(jīng)元是否能讓罹患帕金森氏癥的實(shí)驗(yàn)小鼠和大鼠受益,，如果起作用,，他們將在猴子身上進(jìn)行同樣的實(shí)驗(yàn)。同時(shí),，他們也在對(duì)不使用病毒而對(duì)皮膚細(xì)胞進(jìn)行重組的方法進(jìn)行評(píng)估,，以消除病毒可能會(huì)給人體造成的任何潛在風(fēng)險(xiǎn)。
瑞典蘭德大學(xué)的科研團(tuán)隊(duì)由馬林·帕默所領(lǐng)導(dǎo),，他們首先將從胚胎提取出的人體皮膚細(xì)胞變成神經(jīng)元,，接著變成特定的能制造多巴胺的神經(jīng)元。他們總共使用了5個(gè)轉(zhuǎn)錄因子,，其中包括意大利團(tuán)隊(duì)使用的兩個(gè)轉(zhuǎn)錄因子Mash1和Lmx1a,。帕默表示，他們目前也在測(cè)試使用人體細(xì)胞制成的神經(jīng)元是否能讓罹患帕金森氏癥的動(dòng)物受益,。相關(guān)論文發(fā)表于美國(guó)《國(guó)家科學(xué)院院刊》（PNAS）,。
這兩種新方法都避免了將皮膚細(xì)胞轉(zhuǎn)化為類似于胚胎干細(xì)胞的誘導(dǎo)多能干（iPS）細(xì)胞這個(gè)步驟。iPS細(xì)胞俗稱“皮膚干細(xì)胞”,，是經(jīng)由皮膚細(xì)胞制備而成,，具有分化成其他類型細(xì)胞的能力，但培育iPS細(xì)胞需要依靠病毒載體,，其最大問題是容易形成腫瘤,。（生物谷Bioon.com）
生物谷推薦原文出處：
Nature doi:10.1038/nature10284
Direct generation of functional dopaminergic neurons from mouse and human fibroblasts
Massimiliano Caiazzo; Maria Teresa Dell’Anno; Elena Dvoretskova; Dejan Lazarevic; Stefano Taverna; Damiana Leo; Tatyana D. Sotnikova; Andrea Menegon; Paola Roncaglia; Giorgia Colciago; Giovanni Russo; Piero Carninci; Gianni Pezzoli; Raul R. Gainetdinov; Stefano Gustincich; Alexander Dityatev; Vania Broccoli
Transplantation of dopaminergic neurons can potentially improve the clinical outcome of Parkinson’s disease, a neurological disorder resulting from degeneration of mesencephalic dopaminergic neurons1, 2. In particular, transplantation of embryonic-stem-cell-derived dopaminergic neurons has been shown to be efficient in restoring motor symptoms in conditions of dopamine deficiency3, 4. However, the use of pluripotent-derived cells might lead to the development of tumours if not properly controlled5. Here we identified a minimal set of three transcription factors—Mash1 (also known as Ascl1), Nurr1 (also known as Nr4a2) and Lmx1a—that are able to generate directly functional dopaminergic neurons from mouse and human fibroblasts without reverting to a progenitor cell stage. Induced dopaminergic (iDA) cells release dopamine and show spontaneous electrical activity organized in regular spikes consistent with the pacemaker activity featured by brain dopaminergic neurons. The three factors were able to elicit dopaminergic neuronal conversion in prenatal and adult fibroblasts from healthy donors and Parkinson’s disease patients. Direct generation of iDA cells from somatic cells might have significant implications for understanding critical processes for neuronal development, in vitro disease modelling and cell replacement therapies.
Proceedings of the National Academy of Sciences DOI： 10.1073/pnas.1105135108
Direct conversion of human fibroblasts to dopaminergic neurons
Pfisterer, Ulrich; Kirkeby, Agnete; Torper, Olof; Wood, James; Nelander, Jenny; Dufour, Audrey; Bj?rklund, Anders; Lindvall, Olle; Jakobsson, Johan; Parmar, Malin
Recent reports demonstrate that somatic mouse cells can be directly converted to other mature cell types by using combinedexpression of defined factors. Here we show that the same strategy can be applied to human embryonic and postnatal fibroblasts.By overexpression of the transcription factors Ascl1, Brn2, and Myt1l, human fibroblasts were efficiently converted to functionalneurons. We also demonstrate that the converted neurons can be directed toward distinct functional neurotransmitter phenotypeswhen the appropriate transcriptional cues are provided together with the three conversion factors. By combining expressionof the three conversion factors with expression of two genes involved in dopamine neuron generation, Lmx1a and FoxA2, we could direct the phenotype of the converted cells toward dopaminergic neurons. Such subtype-specific induced neuronsderived from human somatic cells could be valuable for disease modeling and cell replacement therapy.
