Wnt3a-Induced Mesoderm Formation and Cardiomyogenesis in Human Embryonic Stem Cells
Wnt3a-Induced Mesoderm Formation and Cardiomyogenesis in Human Embryonic Stem Cells
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DOI：
10.1002/stem.95
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发表时间：
2009-08-01
期刊：
影响因子：
5.2
通讯作者：
Burcin, Mark
中科院分区：
文献类型：
--
作者：
Tran, Thanh H.;Wang, Xiurong;Burcin, Mark
人胚胎干细胞（hESC）体外分化为纯人心肌细胞（hESCMs）将为进一步创建旨在推进临床前药物开发的细胞模型提供强有力的工具。在这里，我们报告了一种新的分化方法，大大提高hESCM产量。在用Wnt3a早期和瞬时处理hESC后，胚状体和中内胚层形成增强，导致向心肌细胞的更大分化。此外，所产生的搏动簇高度富集心肌细胞（50%）并表达心肌细胞的特征基因，这提供了这些hESCMs能够在体外发育成功能和生理相关心肌细胞的证据。总之，该方案不仅有可能保证丰富的心肌细胞群体的可再生供应，以开发新的和更具预测性的细胞模型，而且还应该为心脏再生的关键途径提供有价值的见解。干细胞2009; 27：1869 - 1878
In vitro differentiation of human embryonic stem cells (hESCs) into pure human cardiomyocytes (hESCMs) would present a powerful tool to further the creation of cell models designed to advance preclinical drug development. Here, we report a novel differentiation method to substantially increase hESCM yield. Upon early and transient treatment of hESCs with Wnt3a, embryoid body and mesendoderm formation is enhanced, leading to greater differentiation toward cardiomyocytes. Moreover, the generated beating clusters are highly enriched with cardiomyocytes (50%) and express genes characteristic of cardiac cells, providing evidence that these hESCMs are competent to develop in vitro into functional and physiologically relevant cardiomyocytes. In summary, this protocol not only has the potential to guarantee a renewable supply of enriched cardiomyocyte populations for developing novel and more predictive cell models, but it also should provide valuable insights into pathways critical for cardiac regeneration. STEM CELLS 2009;27:1869-1878