Kidney specific protein-positive cells derived from embryonic stem cells reproduce tubular structures in vitro and differentiate into renal tubular cells.

Kidney specific protein-positive cells derived from embryonic stem cells reproduce tubular structures in vitro and differentiate into renal tubular cells.
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DOI:
10.1371/journal.pone.0064843
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Itoh H
Itoh H
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Morizane R;Monkawa T;Fujii S;Yamaguchi S;Homma K;Matsuzaki Y;Okano H;Itoh H

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胚胎干细胞和诱导多能干细胞具有向多种器官和组织分化的能力,被认为是阐明疾病机制的新工具,也是再生治疗的来源。然而,迫切需要一种从多能干细胞诱导器官特异性细胞的方法。尽管许多科学家已经开发出从多能干细胞中诱导各种器官特异性细胞的方法,但由于肾脏结构的复杂性和肾脏成分细胞的多样性,仍未在体外诱导出肾系细胞。在这里,我们描述了一种方法,通过使用抗KSP抗体对肾脏特异蛋白(KSP)阳性细胞进行细胞纯化,从小鼠胚胎干细胞中诱导出肾小管细胞。来自ES细胞的KSP阳性细胞的整体基因表达谱表现出与发育中的肾脏细胞相似的特征,当在Matrigel的3D培养中培养时,KSP阳性细胞具有形成类似肾小管细胞的管状结构的能力。此外,我们的结果表明,当WNT4刺激时,KSP阳性细胞通过肾小管形成获得了每段肾小管细胞的特征。这种方法是利用多能干细胞研究肾脏疾病和开发肾脏再生疗法的重要一步。
Embryonic stem cells and induced pluripotent stem cells have the ability to differentiate into various organs and tissues, and are regarded as new tools for the elucidation of disease mechanisms as well as sources for regenerative therapies. However, a method of inducing organ-specific cells from pluripotent stem cells is urgently needed. Although many scientists have been developing methods to induce various organ-specific cells from pluripotent stem cells, renal lineage cells have yet to be induced in vitro because of the complexity of kidney structures and the diversity of kidney-component cells. Here, we describe a method of inducing renal tubular cells from mouse embryonic stem cells via the cell purification of kidney specific protein (KSP)-positive cells using an anti-KSP antibody. The global gene expression profiles of KSP-positive cells derived from ES cells exhibited characteristics similar to those of cells in the developing kidney, and KSP-positive cells had the capacity to form tubular structures resembling renal tubular cells when grown in a 3D culture in Matrigel. Moreover, our results indicated that KSP-positive cells acquired the characteristics of each segment of renal tubular cells through tubular formation when stimulated with Wnt4. This method is an important step toward kidney disease research using pluripotent stem cells, and the development of kidney regeneration therapies.
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