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2008-4-8 9:43:31

PNAS:“皮肤干细胞”能缓解帕金森氏症

美国科研人员日前在新一期美国《国家科学院学报》上报告说,他们发现用成年老鼠皮肤细胞改造而成的“皮肤干细胞”能有效改善老鼠的帕金森氏症症状,从而证实这种干细胞具有与胚胎干细胞类似的治疗功能。

来自美国怀特黑德生物医学研究所的科学家,对老鼠皮肤细胞进行改造,增强了该细胞中若干基因的功能,培育出了一种“皮肤干细胞”。在将这种干细胞移植给患有帕金森氏症的老鼠后,研究者发现,“皮肤干细胞”能逐渐分化发展,最终取代那些受损的神经细胞,使病鼠的帕金森氏症症状明显好转。

报告的作者马里乌斯指出,这项研究说明,“皮肤干细胞”与胚胎干细胞一样,能进入神经系统,对帕金森氏症等神经疾病产生积极作用。

由于胚胎干细胞可以分化成不同种类的体细胞,替换由于疾病而受损的脑细胞,因此一直被认为是治疗帕金森氏症、早老性痴呆症的理想方法。但胚胎干细胞要从人类胚胎中提取,有关研究常遇到伦理方面的指责。

2007年日本京都大学的一个研究小组和美国威斯康星大学麦迪逊分校的研究小组分别宣布,他们利用基因重组技术,成功地将人体皮肤细胞转变成了干细胞。科学界普遍认为,这类研究成果具有划时代意义,可以使人类避开利用胚胎进行干细胞研究的伦理争议,从而大大推动与干细胞有关的疾病疗法研究。

生物谷推荐原始出处

PNAS),10.1073/pnas.0801677105,Marius Wernig, Rudolf Jaenisch

Neurons derived from reprogrammed fibroblasts functionally integrate into the fetal brain and improve symptoms of rats with Parkinson's disease

Marius Wernig*, Jian-Ping Zhao{dagger}, Jan Pruszak{ddagger}, Eva Hedlund{ddagger}, Dongdong Fu*, Frank Soldner*, Vania Broccoli§, Martha Constantine-Paton{dagger}, Ole Isacson{ddagger}, and Rudolf Jaenisch*,||

*The Whitehead Institute for Biomedical Research, Cambridge, MA 02142; {dagger}The McGovern Institute for Brain Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139; {ddagger}Udall Parkinson's Disease Research Center of Excellence and Neuroregeneration Laboratories, McLean Hospital/Harvard University, Belmont, MA 02478; and §San Raffaele Scientific Institute, 20132 Milan, Italy

Contributed by Rudolf Jaenisch, February 21, 2008 (sent for review January 21, 2008)

Abstract

The long-term goal of nuclear transfer or alternative reprogramming approaches is to create patient-specific donor cells for transplantation therapy, avoiding immunorejection, a major complication in current transplantation medicine. It was recently shown that the four transcription factors Oct4, Sox2, Klf4, and c-Myc induce pluripotency in mouse fibroblasts. However, the therapeutic potential of induced pluripotent stem (iPS) cells for neural cell replacement strategies remained unexplored. Here, we show that iPS cells can be efficiently differentiated into neural precursor cells, giving rise to neuronal and glial cell types in culture. Upon transplantation into the fetal mouse brain, the cells migrate into various brain regions and differentiate into glia and neurons, including glutamatergic, GABAergic, and catecholaminergic subtypes. Electrophysiological recordings and morphological analysis demonstrated that the grafted neurons had mature neuronal activity and were functionally integrated in the host brain. Furthermore, iPS cells were induced to differentiate into dopamine neurons of midbrain character and were able to improve behavior in a rat model of Parkinson's disease upon transplantation into the adult brain. We minimized the risk of tumor formation from the grafted cells by separating contaminating pluripotent cells and committed neural cells using fluorescence-activated cell sorting. Our results demonstrate the therapeutic potential of directly reprogrammed fibroblasts for neuronal cell replacement in the animal model.

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