Pathway decision-making strategies for generating pancreatic beta-cells: systems biology or hit and miss?
Pathway decision-making strategies for generating pancreatic beta-cells: systems biology or hit and miss?
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DOI：
10.1097/med.0b013e32827035dd
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发表时间：
2007-08-01
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影响因子：
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通讯作者：
Jensen, Jan
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文献类型：
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作者：
Jensen, Jan
审查目的：方法选择策略，以实现β-细胞分化从人胚胎干细胞review.Recent发现：期望很高的胚胎干细胞衍生的细胞替代方法来治愈糖尿病，最近的观察表明，成熟的β-细胞可以来自人胚胎干细胞。然而，就转化背景而言，我们还没有达到这个水平;胚胎干细胞转化为完全成熟的β细胞并不有效，也没有提供一个独特的β细胞群体作为最终产品。总结：研究强调，期待开发一种促进内分泌命运的“神奇媒体子弹”是相当乐观的;连续给予信号诱导剂，仔细提供以模拟正常发育，更有可能成功。为了完成这一任务，我们需要更好地了解细胞外信号通路，推动渐进的内胚层命运的选择在整个发展。胰腺中命运分配的细胞内在控制的知识正在迅速增长。然而，有关内胚层和胰腺中的形态发生密码子的信息不足，阻碍了未定型胚胎干细胞向内胚层、胰腺和随后的内分泌特异性命运的更好的定向分化模式的发展。一个系统的方法来定义发育中的内胚层和胰腺的形态发生代码出现及时和合理的。
PURPOSE OF REVIEW: Method selection strategies to achieve beta-cell differentiation from human embryonic stem cells are reviewed.RECENT FINDINGS: Expectations are high for an embryonic stem cell derived cellular replacement method to cure diabetes, and recent observations indicate that mature beta-cells can be derived from human embryonic stem cells. In terms of the translational setting, however, we are not there yet; conversion of embryonic stem cells to fully mature beta-cells is not effective and does not provide an exclusive beta-cell population as the end-product.SUMMARY: Studies emphasize that expecting development of a 'magic media bullet' that promotes endocrine fate is rather optimistic; consecutive administration of signaling inducers, carefully provided to mimic normal development, is more likely to succeed. To accomplish this task we need better understanding of the extracellular signaling pathways that drive progressive endodermal fate choices throughout development. Knowledge of cell-intrinsic control of fate assignments in pancreas is growing rapidly. Nevertheless, insufficient information regarding morphogen codes that operate in endoderm and pancreas is hindering development of better, directed differentiation schema of uncommitted embryonic stem cells toward endodermal, pancreatic, and subsequent endocrine specific fates. A systematic approach to defining morphogen codes in developing endoderm and pancreas appears timely and justified.