Generation of functional gut-like organ from mouse induced pluripotent stem cells
Generation of functional gut-like organ from mouse induced pluripotent stem cells
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DOI：
10.1016/j.bbrc.2009.10.157
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发表时间：
2010-01-01
影响因子：
3.1
通讯作者：
Nakajima, Yoshiyuki
中科院分区：
文献类型：
--
作者：
Ueda, Takeshi;Yamada, Takatsugu;Nakajima, Yoshiyuki
诱导多能干细胞（iPS）具有分化为所有三个胚胎胚层的广谱衍生物的多能性。然而，iPS细胞组织复杂和功能性“器官”的体外器官分化潜力尚未得到证实。在这里，我们证明了小鼠iPS细胞有能力组织一个肠道样器官的运动功能，在体外的悬滴培养系统。这种“诱导肠道（iGut）”表现出自发收缩和高度协调的消化，伴随着内容物的运输。超微结构分析确定iGut具有由三个不同层（上皮、结缔组织和肌肉组织）包围的大管腔。c-Kit是Cajal间质细胞（ICCs，肠道起搏细胞）的一种，在肠腔壁有明显的免疫反应，并形成一个明显而密集的网络。神经丝免疫反应可形成大的神经节样结构和密集的神经元网络。iGut由三个胚层的所有肠组分组成：上皮细胞（内胚层）、平滑肌细胞（中胚层）、ICC（中胚层）。和肠神经元（外胚层）这是首次报道证明iPS细胞体外分化为特定类型的功能性“器官”的潜能。这项工作不仅有助于通过疾病特异性iPS细胞了解无法治愈的肠道疾病的机制，而且还有助于患者特异性iPS细胞在未来用于新型治疗策略（如患者特异性“器官”再生医学）的临床应用。(C)2009 Elsevier Inc. All rights reserved.
Induced pluripotent stem (iPS) cells have the pluripotency to differentiate into broad spectrum derivatives of all three embryonic germ layers However, the in vitro organ differentiation potential of iPS cells to organize a complex and functional "organ" has not yet been demonstrated. Here, we demonstrate that mouse iPS cells have the ability to organize a gut-like organ with motor function in vitro by a hanging drop culture system. This "induced gut (iGut)" exhibited spontaneous contraction and highly coordinated peristalsis accompanied by a transportation of contents. Ultrastructural analysis identified that the iGut had large lumens surrounded by three distinct layers (epithelium, connective tissue and Musculature). Immunoreactivity for c-Kit, a market of interstitial cells of Cajal (ICCs, enteric pacemaker cells), was observed in the wall of the lumen and formed a distinct and dense network The neurofilament immunoreactivity was identified to form large ganglion-like structures and dense neuronal networks. The iGut was composed of all the enteric components of three germ layers: epithelial cells (endoderm), smooth muscle cells (mesoderm), ICCs (mesoderm). and enteric neurons (ectoderm) This is the first report to demonstrate the in vitro differentiation potential of iPS cells into particular types of functional "organs." This work not only contributes to understanding the mechanisms of incurable gut disease through disease-specific iPS cells, but also facilitates the clinical application of patient-specific iPS cells for novel therapeutic strategies such as patient-specific "organ" regenerative medicine in the future. (C) 2009 Elsevier Inc. All rights reserved.