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比较诱导多能干细胞与胚胎干细胞体外分化为少突胶质细胞的效率。

Comparison of efficiency of terminal differentiation of oligodendrocytes from induced pluripotent stem cells versus embryonic stem cells in vitro.

机构信息

Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.

出版信息

J Biosci Bioeng. 2010 Jun;109(6):622-8. doi: 10.1016/j.jbiosc.2009.11.013. Epub 2009 Dec 14.

DOI:10.1016/j.jbiosc.2009.11.013
PMID:20471604
Abstract

Oligodendrocytes are the myelinating cells of the central nervous system (CNS), and defects in these cells can result in the loss of CNS functions. Although oligodendrocyte progenitor cells transplantation therapy is an effective cure for such symptoms, there is no readily available source of these cells. Recent studies have described the generation of induced pluripotent stem cells (iPS cells) from somatic cells, leading to anticipation of this technique as a novel therapeutic tool in regenerative medicine. In this study, we evaluated the ability of iPS cells derived from mouse embryonic fibroblasts to differentiate into oligodendrocytes and compared this with the differential ability of mouse embryonic stem cells (ES cells). Experiments using an in vitro oligodendrocyte differentiation protocol that was optimized to ES cells demonstrated that 2.3% of iPS cells differentiated into O4(+) oligodendrocytes compared with 24.0% of ES cells. However, the rate of induction of A2B5(+) oligodendrocyte precursor cell (OPC) was similar for both iPS-derived cells and ES-derived cells (14.1% and 12.6%, respectively). These findings suggest that some intracellular factors in iPS cells inhibit the terminal differentiation of oligodendrocytes from the OPC stage.

摘要

少突胶质细胞是中枢神经系统(CNS)的髓鞘形成细胞,这些细胞的缺陷可导致 CNS 功能丧失。尽管少突胶质前体细胞移植治疗是治疗此类症状的有效方法,但目前还没有这些细胞的现成来源。最近的研究描述了从体细胞中产生诱导多能干细胞(iPS 细胞),这使得人们期待这项技术成为再生医学中的一种新型治疗工具。在这项研究中,我们评估了源自小鼠胚胎成纤维细胞的 iPS 细胞分化为少突胶质细胞的能力,并将其与小鼠胚胎干细胞(ES 细胞)的分化能力进行了比较。使用针对 ES 细胞优化的体外少突胶质细胞分化方案进行的实验表明,与 ES 细胞的 24.0%相比,iPS 细胞分化为 O4(+)少突胶质细胞的比例为 2.3%。然而,iPS 细胞和 ES 细胞来源的细胞诱导 A2B5(+)少突胶质前体细胞(OPC)的比率相似(分别为 14.1%和 12.6%)。这些发现表明,iPS 细胞中的一些细胞内因素抑制了 OPC 阶段少突胶质细胞的终末分化。

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