Human embryonic stem cells: Genetic manipulation on the way to cardiac cell therapies
Human embryonic stem cells: Genetic manipulation on the way to cardiac cell therapies
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DOI：
10.1016/j.reprotox.2005.04.012
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发表时间：
2005-09-01
影响因子：
3.3
通讯作者：
Mummery, CL
中科院分区：
文献类型：
--
作者：
Moore, JC;van Laake, LW;Mummery, CL
在它们第一次从人类胚胎中衍生出来近7年后，实现基于人类胚胎干细胞(HESC)的治疗承诺的紧迫性已经出现。已开发出支持未分化细胞的长期生长和部分定向分化为特定细胞系的方案。下一步的阶段几乎已经准备就绪：在人类疾病的动物模型中进行移植。在这里，我们回顾了胚胎干细胞来源的心脏细胞在动物体内移植的最新进展。影响这一领域进展和整体体内功能分析的一个问题是基因标记的hESC的可用性。只有几个细胞株普遍表达报告基因，而且没有一个与特定的谱系相关；一个主要的障碍是hESC对既定的感染和化学导入异源基因的方法的抵抗力。对已取得成功的方法进行了综述。我们还描述了构建一种新的、基因修饰的hESC株的过程，该细胞系组成地表达GFP以及它的一些特征，包括它形成具有室样细胞电生理特性的心肌细胞的能力。(C)2005 Elsevier Inc.保留所有权利。
Almost 7 years after their first derivation from human embryos, a pressing urgency to deliver the promises of therapies based on human embryonic stem cells (hESC) has arisen. Protocols have been developed to support long-term growth of undifferentiated cells and partially direct differentiation to specific cell lineages. The stage has almost been set for the next step: transplantation in animal models of human disease. Here, we review the state-of-the-art with respect to the transplantation of embryonic stem cell-derived heart cells in animals. One problem affecting progress in this area and functional analysis in vivo in general, is the availability of genetically marked hESC. There are only a few cell lines that express reporter genes ubiquitously, and none is associated with particular lineages; a major hurdle has been the resistance of hESC to established infection and chemical transfection methodologies to introduce ectopic genes. The methods that have been successful are reviewed. We also describe the processes for generating a new, genetically-modified hESC line that constitutively expresses GFP as well as some of its characteristics, including its ability to form cardiomyocytes with electrophysiological properties of ventricular-like cells. (c) 2005 Elsevier Inc. All rights reserved.