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人骨髓间充质干细胞中神经突生长诱导的信号通路。

Signalling pathway in the induction of neurite outgrowth in human mesenchymal stem cells.

作者信息

Chu Mien-Sheng, Chang Ching-Fang, Yang Chuan-Ching, Bau Yi-Chi, Ho Larry Low-Tone, Hung Shih-Chieh

机构信息

Stem Cell Laboratory, Medical Research and Education, Veterans General Hospital-Taipei, Taipei, Taiwan, ROC.

出版信息

Cell Signal. 2006 Apr;18(4):519-30. doi: 10.1016/j.cellsig.2005.05.018. Epub 2005 Aug 11.

DOI:10.1016/j.cellsig.2005.05.018
PMID:16098715
Abstract

Recent in vivo transplantation studies have shown that mesenchymal stem cells (MSCs) were able to differentiate into mesoderm-derived cell types as well as cells with neuroectodermal characteristics, suggesting that transdifferentiation occurs in the mammalian system. We have reported an immortalized line of human MSCs (hMSCs), KP-hMSCs, which expresses CD29, CD44, CD90, and CD105, and complies with the characteristics shared by mere hMSCs. In a current experiment, we further demonstrated that expanded KP-hMSCs exhibited markers of neuroepithelial or neural precursor cells, such as Nestin, Musashi-1, Vimentin, NCAM, Pax-6, and Sox-9. KP-hMSCs simultaneously expressed proteins of the neuronal, astrocyte, and oligodendrocyte lineages during culture expansion; in addition, they initiated neurite outgrowth and eradicated protein expressions of astrocyte and oligodendrocyte lineages in response to the elevated signaling of the cAMP-PKA pathway after serum depletion in a defined neural induction medium. From the current results, KP-hMSCs may be used to elucidate molecular signaling on the neural differentiation of adult human non-neural tissues. We also presented evidence for the possibility that adult MSCs and fetal neuroepithelial or neural precursor cells both provide for the continual maintenance and repair of the postnatal neural tissues and may derive from the same origin or have one deriving from the other.

摘要

最近的体内移植研究表明,间充质干细胞(MSC)能够分化为中胚层来源的细胞类型以及具有神经外胚层特征的细胞,这表明转分化发生在哺乳动物系统中。我们报道了一种永生化的人MSC系(hMSC),即KP-hMSC,它表达CD29、CD44、CD90和CD105,符合单纯hMSC共有的特征。在当前实验中,我们进一步证明,扩增后的KP-hMSC表现出神经上皮或神经前体细胞的标志物,如巢蛋白、神经保护素1、波形蛋白、神经细胞黏附分子、配对盒基因6和性别决定区Y框蛋白9。在培养扩增过程中,KP-hMSC同时表达神经元、星形胶质细胞和少突胶质细胞谱系的蛋白;此外,在特定的神经诱导培养基中血清耗尽后,它们响应cAMP-PKA途径升高的信号,开始长出神经突并消除星形胶质细胞和少突胶质细胞谱系的蛋白表达。根据当前结果,KP-hMSC可用于阐明成人非神经组织神经分化的分子信号。我们还提供了证据,证明成人MSC与胎儿神经上皮或神经前体细胞都为出生后神经组织的持续维持和修复提供支持,并且可能起源相同或其中一个起源于另一个。

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