據(jù)英國《新科學家》雜志網站近日報道,,兩個科研小組分別宣布,,他們對老鼠皮膚細胞和人類皮膚細胞進行基因重組,,將其變成了能制造多巴胺的特定神經元。未來,,帕金森氏癥患者有望借助用自己的皮膚制成的神經元來醫(yī)治自己的病癥,。
科學家們表示,,在帕金森氏癥患者大腦內,多巴胺這種對人的活動能力至關重要的神經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整大腦內多巴胺的濃度,但成功率因個體差異有高有低,。而新研究表明,,通過將患者自身的皮膚細胞變?yōu)樯窠浽獊碇圃於喟桶罚怪诖竽X內的濃度恢復至正常水平,,可改善患者的運動能力,。
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轉錄因子(同神經元的發(fā)育有關的蛋白質),對實驗老鼠的皮膚細胞進行了重組,。同樣的三個轉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提取而來的皮膚細胞變成神經元。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錄因子的病毒來感染皮膚細胞,,盡管使用病毒并不會破壞DNA(脫氧核糖核酸),也不會引發(fā)癌癥,。相關論文發(fā)表于《自然》(Nature)雜志,。
波切利表示,他的團隊正在測試,,用實驗鼠細胞以及人體細胞制成的神經元是否能讓罹患帕金森氏癥的實驗小鼠和大鼠受益,,如果起作用,他們將在猴子身上進行同樣的實驗,。同時,,他們也在對不使用病毒而對皮膚細胞進行重組的方法進行評估,以消除病毒可能會給人體造成的任何潛在風險,。
瑞典蘭德大學的科研團隊由馬林·帕默所領導,,他們首先將從胚胎提取出的人體皮膚細胞變成神經元,接著變成特定的能制造多巴胺的神經元,。他們總共使用了5個轉錄因子,,其中包括意大利團隊使用的兩個轉錄因子Mash1和Lmx1a。帕默表示,,他們目前也在測試使用人體細胞制成的神經元是否能讓罹患帕金森氏癥的動物受益,。相關論文發(fā)表于美國《國家科學院院刊》(PNAS)。
這兩種新方法都避免了將皮膚細胞轉化為類似于胚胎干細胞的誘導多能干(iPS)細胞這個步驟,。iPS細胞俗稱“皮膚干細胞”,,是經由皮膚細胞制備而成,具有分化成其他類型細胞的能力,,但培育iPS細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.