美国戴维·格拉斯通研究所的科学家丁盛（音译）报告称，他通过细胞重组技术，对现有的诱导多能干细胞(iPS细胞)技术进行改进，将成人皮肤细胞直接转化成了神经干细胞，新方法在再生医学领域具有重要的应用潜力。相关研究发表于4月25日出版的《美国国家科学院院刊》上。
人类胚胎干细胞是一种多功能细胞，能发育成人体内任何类型的细胞，因此在再生医学领域拥有巨大的应用潜力。很多科学家认为，未来可以使用人类胚胎干细胞治疗和根除心脏病、糖尿病和帕金森氏症等多种疾病。然而，由于获取人类胚胎干细胞需要使用人类早期胚胎，相关研究一直饱受伦理方面的指责和争议。
格拉斯通研究所的山中伸弥为了克服使用人类胚胎干细胞面临的挑战，培育出iPS细胞。iPS细胞源于病人自己的皮肤细胞，其作用同胚胎干细胞类似，但却拥有胚胎干细胞不具备的优势，可被用于个性化医疗,免除移植可能会引发的风险,同时还能避免胚胎干细胞面临的伦理问题。
在最新的细胞重组研究中，丁盛对iPS细胞技术进行了些许改进，通过重组将皮肤细胞直接变成了神经干细胞。丁盛的方法是让iPS细胞不进入可发育成任何类型的细胞的多功能状态。避免多功能状态非常重要，因为，它避免了被用来替代或修复受损器官或组织时，有些iPS细胞会发育成肿瘤的潜在风险。
所得到的神经干细胞是一类具有分裂潜能和自更新能力的母细胞，可以通过不对等的分裂方式产生神经组织的各类细胞。这种细胞重组技术也使科学家能制造出更多的细胞以用于科学研究和再生医学领域。
丁盛表示，这些细胞还无法用于移植，但新技术消除了利用iPS细胞制造可以移植的细胞以治疗多种疾病所面临的一些主要障碍。（生物谷Bioon.com）
生物谷推荐原文出处：
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.
