2012年10月23日 訊 /生物谷BIOON/ --研究人員發(fā)現(xiàn)一種新的方法來(lái)將我們大腦中發(fā)現(xiàn)的一種類(lèi)型的成體細(xì)胞轉(zhuǎn)化為新的人神經(jīng)元。這項(xiàng)發(fā)現(xiàn)為開(kāi)發(fā)出細(xì)胞療法來(lái)治療諸如阿爾茨海默病和帕金森病值來(lái)的神經(jīng)退化性疾病奠定基礎(chǔ),。相關(guān)研究結(jié)果于近期刊登在Cell Stem Cell期刊上,。
論文通訊作者Benedikt Berninger說(shuō)，“這項(xiàng)研究旨在把在整個(gè)大腦都存在的除了神經(jīng)元之外的細(xì)胞轉(zhuǎn)化為神經(jīng)元,。我們所考慮的最終目標(biāo)是這可能有朝一日能夠讓我們?cè)诖竽X內(nèi)誘導(dǎo)這種轉(zhuǎn)化,，因而提供一種新的策略來(lái)修復(fù)受損或患病的大腦。”
在這項(xiàng)研究中,，用來(lái)從一種身份轉(zhuǎn)換為另一種身份的細(xì)胞是周皮細(xì)胞(pericyte),。這些細(xì)胞與血管密切相關(guān)聯(lián)，在維持血腦屏障完整中發(fā)揮著重要作用,，而且還被證實(shí)參與身體其他部分的傷口愈合,。
Berninger說(shuō)，“如今,，我們推斷,，如果我們能夠靶向并誘導(dǎo)它們轉(zhuǎn)化為神經(jīng)細(xì)胞，那么我們就能夠利用這種損傷反應(yīng),。”
進(jìn)一步測(cè)試表明這些新形成的神經(jīng)元能夠產(chǎn)生電信號(hào),，并且延伸到其他的神經(jīng)元，這就證實(shí)這些新形成的系細(xì)胞能夠整合進(jìn)神經(jīng)網(wǎng)絡(luò)之中,。
研究人員寫(xiě)道,，“盡管人們還需更多地了解關(guān)于在體內(nèi)利用一種直接的神經(jīng)元重編程策略進(jìn)行有意義的修復(fù)方面的信息，但是我們的研究強(qiáng)烈地支持這種觀點(diǎn)在受損大腦內(nèi)對(duì)周皮細(xì)胞來(lái)源的細(xì)胞進(jìn)行神經(jīng)元重編程可能變成一種可行的方法來(lái)替換發(fā)生退化的神經(jīng)元,。”(生物谷Bioon.com)
doi: 10.1016/j.stem.2012.07.007
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Reprogramming of Pericyte-Derived Cells of the Adult Human Brain into Induced Neuronal Cells
Marisa Karow, Rodrigo Sánchez, Christian Schichor, Giacomo Masserdotti, Felipe Ortega, Christophe Heinrich, Sergio Gascón, Muhammad A. Khan, D. Chichung Lie, Arianna Dellavalle, Giulio Cossu, Roland Goldbrunner, Magdalena Götz, Benedikt Berninger
Reprogramming of somatic cells into neurons provides a new approach toward cell-based therapy of neurodegenerative diseases. A major challenge for the translation of neuronal reprogramming into therapy is whether the adult human brain contains cell populations amenable to direct somatic cell conversion. Here we show that cells from the adult human cerebral cortex expressing pericyte hallmarks can be reprogrammed into neuronal cells by retrovirus-mediated coexpression of the transcription factors Sox2 and Mash1. These induced neuronal cells acquire the ability of repetitive action potential firing and serve as synaptic targets for other neurons, indicating their capability of integrating into neural networks. Genetic fate-mapping in mice expressing an inducible Cre recombinase under the tissue-nonspecific alkaline phosphatase promoter corroborated the pericytic origin of the reprogrammed cells. Our results raise the possibility of functional conversion of endogenous cells in the adult human brain to induced neuronal fates.
