Differentiation of insulin-producing cells from human neural progenitor cells.
Differentiation of insulin-producing cells from human neural progenitor cells.
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DOI：
10.1371/journal.pmed.0020103
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发表时间：
2005-04
期刊：
影响因子：
15.8
通讯作者：
Kim SK
中科院分区：
文献类型：
--
作者：
Hori Y;Gu X;Xie X;Kim SK
基于胰岛移植的 1 型糖尿病疗法的成功，加上全球范围内可供移植的胰岛短缺，促使人们努力开发可再生的胰岛替代组织来源。胰岛和神经元具有共同的特征，包括共同的发育程序，并且在某些物种中，脑神经元是全身胰岛素的主要来源。在这里，我们展示了脑源性人类神经祖细胞，暴露于一系列调节体内胰岛发育的信号，形成葡萄糖反应性胰岛素生成细胞（IPC）簇。在用这种新方法对神经祖细胞进行体外分化的过程中，编码胰岛发育的必需的已知体内调节因子的基因被表达。移植到免疫功能低下的小鼠体内后，IPCs 在葡萄糖激发后释放胰岛素 C 肽，保持分化，并且没有形成可检测到的肿瘤。在没有基因操作的情况下仅通过细胞外因子调节来生产IPC可能会促进从人类神经祖细胞和其他类型的多能人类干细胞中衍生出可移植的胰岛替代组织的策略。寻找能够分泌胰岛素的细胞不必局限于胰腺前体细胞；来自神经祖细胞的细胞也可以产生胰岛素并对葡萄糖做出反应
Success in islet-transplantation-based therapies for type 1 diabetes, coupled with a worldwide shortage of transplant-ready islets, has motivated efforts to develop renewable sources of islet-replacement tissue. Islets and neurons share features, including common developmental programs, and in some species brain neurons are the principal source of systemic insulin. Here we show that brain-derived human neural progenitor cells, exposed to a series of signals that regulate in vivo pancreatic islet development, form clusters of glucose-responsive insulin-producing cells (IPCs). During in vitro differentiation of neural progenitor cells with this novel method, genes encoding essential known in vivo regulators of pancreatic islet development were expressed. Following transplantation into immunocompromised mice, IPCs released insulin C-peptide upon glucose challenge, remained differentiated, and did not form detectable tumors. Production of IPCs solely through extracellular factor modulation in the absence of genetic manipulations may promote strategies to derive transplantable islet-replacement tissues from human neural progenitor cells and other types of multipotent human stem cells. The search for cells that can secrete insulin need not be limited to pancreatic precursors; cells derived from neural progenitors can also produce insulin and respond to glucose
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影响因子：
6.2
作者：
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通讯作者：
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影响因子：
30.8
作者：
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