2012年9月28日 訊 /生物谷BIOON/ --來(lái)自新西蘭奧克蘭大學(xué)大腦研究中心的研究人員成功地將人皮膚細(xì)胞直接地轉(zhuǎn)化為不成熟的腦細(xì)胞或者說(shuō)神經(jīng)前體細(xì)胞(neural precursor cell),。他們開發(fā)出一種快速和有效的方法來(lái)完成這種轉(zhuǎn)化，同時(shí)也不用經(jīng)歷轉(zhuǎn)化為類似胚胎干細(xì)胞的誘導(dǎo)性多能干細(xì)胞中間階段,。
Bronwen Connor說(shuō),，“對(duì)全世界的干細(xì)胞研究而言，這是一次具有重大意義的進(jìn)步,。它有潛力導(dǎo)致人們對(duì)諸如亨丁頓舞蹈癥,、帕金森病和阿爾茨海默病之類的神經(jīng)退化疾病產(chǎn)生新的認(rèn)識(shí)。”
這項(xiàng)研究的一個(gè)主要優(yōu)勢(shì)在于,，它能夠讓探究人員從患有基因相關(guān)性神經(jīng)系統(tǒng)疾病的病人體內(nèi)采集皮膚細(xì)胞,，然后利用這些細(xì)胞構(gòu)建出受這些疾病影響的腦細(xì)胞。這將有助于人們深入理解導(dǎo)致這些疾病的機(jī)制,。它將允許人們?cè)诖竽X組織上測(cè)試潛在的治療方法,。它也將允許人們?cè)谖磥?lái)有可能替代受損的腦細(xì)胞。
盡管全世界的許多研究小組也正在研究將皮膚細(xì)胞轉(zhuǎn)化為腦細(xì)胞的新方法,，但是在當(dāng)前這項(xiàng)研究中,，奧克蘭大學(xué)大腦研究中心研究人員開發(fā)出的這種方法是比較獨(dú)特的,。首先，他們是僅有的一個(gè)研究小組利用將成年人皮膚細(xì)胞直接轉(zhuǎn)化為腦細(xì)胞,，而其他的研究小組正在利用這種技術(shù)研究動(dòng)物皮膚細(xì)胞,。其次，奧克蘭大學(xué)研究小組正在使用僅僅兩個(gè)基因SOX2和PAX6就能夠?qū)⑵つw細(xì)胞重編程為神經(jīng)前體細(xì)胞,，而其他國(guó)際研究小組正在使用5到11個(gè)基因,。
這些研究發(fā)現(xiàn)的一個(gè)影響就是加快重編程過(guò)程。將皮膚細(xì)胞先轉(zhuǎn)化為誘導(dǎo)性多能干細(xì)胞再轉(zhuǎn)化為神經(jīng)前體細(xì)胞需要4個(gè)月的時(shí)間,。如果皮膚細(xì)胞能夠被直接轉(zhuǎn)化為神經(jīng)前體細(xì)胞,，那么根據(jù)所使用的技術(shù)類型，它只需一個(gè)半月或20天的時(shí)間,。研究人員開發(fā)出的這種系統(tǒng)也是非常有效的,，從而導(dǎo)致一種細(xì)胞類型高效地轉(zhuǎn)化為另一種類型。而這種直接轉(zhuǎn)化也能夠克服使用胚胎干細(xì)胞或誘導(dǎo)性多能干細(xì)胞時(shí)能夠?qū)е履[瘤形成的問(wèn)題,。
相關(guān)研究結(jié)果于近期刊登在Journal of Stem Cells & Regenerative Medicine期刊上,。(生物谷Bioon.com)
doi: e008030300001
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Non-Viral Generation of Neural Precursor-like Cells from Adult Human Fibroblasts
Maucksch C1, Firmin E1, Butler-Munro C2, Montgomery JM2, Dottori M3, Connor B1
Recent studies have reported direct reprogramming of human fibroblasts to mature neurons by the introduction of defined neural genes. This technology has potential use in the areas of neurological disease modeling and drug development. However, use of induced neurons for large-scale drug screening and cell-based replacement strategies is limited due to their inability to expand once reprogrammed. We propose it would be more desirable to induce expandable neural precursor cells directly from human fibroblasts. To date several pluripotent and neural transcription factors have been shown to be capable of converting mouse fibroblasts to neural stem/precursor-like cells when delivered by viral vectors. Here we extend these findings and demonstrate that transient ectopic insertion of the transcription factors SOX2 and PAX6 to adult human fibroblasts through use of non-viral plasmid transfection or protein transduction allows the generation of induced neural precursor (iNP) colonies expressing a range of neural stem and pro-neural genes. Upon differentiation, iNP cells give rise to neurons exhibiting typical neuronal morphologies and expressing multiple neuronal markers including tyrosine hydroxylase and GAD65/67. Importantly, iNP-derived neurons demonstrate electrophysiological properties of functionally mature neurons with the capacity to generate action potentials. In addition, iNP cells are capable of differentiating into glial fibrillary acidic protein (GFAP)-expressing astrocytes. This study represents a novel virus-free approach for direct reprogramming of human fibroblasts to a neural precursor fate.
