美國(guó)戴維·格拉斯通研究所的科學(xué)家丁盛（音譯）報(bào)告稱,，他通過細(xì)胞重組技術(shù)，對(duì)現(xiàn)有的誘導(dǎo)多能干細(xì)胞(iPS細(xì)胞)技術(shù)進(jìn)行改進(jìn),，將成人皮膚細(xì)胞直接轉(zhuǎn)化成了神經(jīng)干細(xì)胞,，新方法在再生醫(yī)學(xué)領(lǐng)域具有重要的應(yīng)用潛力。相關(guān)研究發(fā)表于4月25日出版的《美國(guó)國(guó)家科學(xué)院院刊》上,。
人類胚胎干細(xì)胞是一種多功能細(xì)胞,，能發(fā)育成人體內(nèi)任何類型的細(xì)胞，因此在再生醫(yī)學(xué)領(lǐng)域擁有巨大的應(yīng)用潛力,。很多科學(xué)家認(rèn)為,，未來可以使用人類胚胎干細(xì)胞治療和根除心臟病、糖尿病和帕金森氏癥等多種疾病,。然而,，由于獲取人類胚胎干細(xì)胞需要使用人類早期胚胎，相關(guān)研究一直飽受倫理方面的指責(zé)和爭(zhēng)議,。
格拉斯通研究所的山中伸彌為了克服使用人類胚胎干細(xì)胞面臨的挑戰(zhàn),，培育出iPS細(xì)胞。iPS細(xì)胞源于病人自己的皮膚細(xì)胞,，其作用同胚胎干細(xì)胞類似,，但卻擁有胚胎干細(xì)胞不具備的優(yōu)勢(shì)，可被用于個(gè)性化醫(yī)療,免除移植可能會(huì)引發(fā)的風(fēng)險(xiǎn),同時(shí)還能避免胚胎干細(xì)胞面臨的倫理問題,。
在最新的細(xì)胞重組研究中,，丁盛對(duì)iPS細(xì)胞技術(shù)進(jìn)行了些許改進(jìn)，通過重組將皮膚細(xì)胞直接變成了神經(jīng)干細(xì)胞,。丁盛的方法是讓iPS細(xì)胞不進(jìn)入可發(fā)育成任何類型的細(xì)胞的多功能狀態(tài),。避免多功能狀態(tài)非常重要，因?yàn)?，它避免了被用來替代或修?fù)受損器官或組織時(shí),，有些iPS細(xì)胞會(huì)發(fā)育成腫瘤的潛在風(fēng)險(xiǎn)。
所得到的神經(jīng)干細(xì)胞是一類具有分裂潛能和自更新能力的母細(xì)胞,，可以通過不對(duì)等的分裂方式產(chǎn)生神經(jīng)組織的各類細(xì)胞,。這種細(xì)胞重組技術(shù)也使科學(xué)家能制造出更多的細(xì)胞以用于科學(xué)研究和再生醫(yī)學(xué)領(lǐng)域。
丁盛表示,，這些細(xì)胞還無法用于移植，但新技術(shù)消除了利用iPS細(xì)胞制造可以移植的細(xì)胞以治療多種疾病所面臨的一些主要障礙,。（生物谷Bioon.com）
生物谷推薦原文出處：
PNAS doi: 10.1073/pnas.1103113108
Direct reprogramming of mouse fibroblasts to neural progenitors
Janghwan Kima,b, Jem A. Efea, Saiyong Zhua, Maria Talantovac, Xu Yuana, Shufen Wangd,e, Stuart A. Liptonc, Kang Zhangd,e, and Sheng Dinga,f,1
Abstract
The simple yet powerful technique of induced pluripotency may eventually supply a wide range of differentiated cells for cell therapy and drug development. However, making the appropriate cells via induced pluripotent stem cells (iPSCs) requires reprogramming of somatic cells and subsequent redifferentiation. Given how arduous and lengthy this process can be, we sought to determine whether it might be possible to convert somatic cells into lineage-specific stem/progenitor cells of another germ layer in one step, bypassing the intermediate pluripotent stage. Here we show that transient induction of the four reprogramming factors (Oct4, Sox2, Klf4, and c-Myc) can efficiently transdifferentiate fibroblasts into functional neural stem/progenitor cells (NPCs) with appropriate signaling inputs. Compared with induced neurons (or iN cells, which are directly converted from fibroblasts), transdifferentiated NPCs have the distinct advantage of being expandable in vitro and retaining the ability to give rise to multiple neuronal subtypes and glial cells. Our results provide a unique paradigm for iPSC-factor–based reprogramming by demonstrating that it can be readily modified to serve as a general platform for transdifferentiation.
PNAS doi: 10.1073/pnas.1014041108
Rapid induction and long-term self-renewal of primitive neural precursors from human embryonic stem cells by small molecule inhibitors
Wenlin Lia,b, Woong Sunc,d, Yu Zhanga, Wanguo Weia, Rajesh Ambasudhana, Peng Xiae, Maria Talantovae, Tongxiang Lina, Janghwan Kima, Xiaolei Wangc, Woon Ryoung Kimd, Stuart A. Liptone, Kang Zhangc,f,1, and Sheng Dinga,g,1
Abstract
Human embryonic stem cells (hESCs) hold enormous promise for regenerative medicine. Typically, hESC-based applications would require their in vitro differentiation into a desirable homogenous cell population. A major challenge of the current hESC differentiation paradigm is the inability to effectively capture and, in the long-term, stably expand primitive lineage-specific stem/precursor cells that retain broad differentiation potential and, more importantly, developmental stage-specific differentiation propensity. Here, we report synergistic inhibition of glycogen synthase kinase 3 (GSK3), transforming growth factor β (TGF-β), and Notch signaling pathways by small molecules can efficiently convert monolayer cultured hESCs into homogenous primitive neuroepithelium within 1 wk under chemically defined condition. These primitive neuroepithelia can stably self-renew in the presence of leukemia inhibitory factor, GSK3 inhibitor (CHIR99021), and TGF-β receptor inhibitor (SB431542); retain high neurogenic potential and responsiveness to instructive neural patterning cues toward midbrain and hindbrain neuronal subtypes; and exhibit in vivo integration. Our work uniformly captures and maintains primitive neural stem cells from hESCs.
