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人胚胎干细胞向心肌细胞的分化及其在体内外的应用。

Differentiation of human embryonic stem cells to cardiomyocytes for in vitro and in vivo applications.

机构信息

Cellartis AB, Arvid Wallgrens Backe 20, SE-413 46, Göteborg, Sweden.

出版信息

Stem Cell Rev Rep. 2010 Mar;6(1):108-20. doi: 10.1007/s12015-010-9113-x.

Abstract

The ability of human embryonic stem cells to differentiate into spontaneously contracting cardiomyocyte-like cells has attracted substantial interest from the scientific community over the last decade. From having been difficult to control, human cardiomyogenesis in vitro is now becoming a process which, to a certain extent, can be effectively manipulated and directed. Although much research remains, new and improved protocols for guiding pluripotent stem cells to the cardiomyocyte lineage are accumulating in the scientific literature. However, the stem cell derived cardiomyocytes described to date, generally resemble immature embryonic/fetal cardiomyocytes, and they are in some functional and structural aspects different from adult cardiomyocytes. Thus, a future challenge will be to design strategies that eventually may allow the cells to reach a higher degree of maturation in vitro. Nevertheless, the cells which can be prepared using current protocols still have wide spread utility, and they have begun to find their way into the drug discovery platforms used in the pharmaceutical industry. In addition, stem cell derived cardiomyocytes and cardiac progenitors are anticipated to have a tremendous impact on how heart disease will be treated in the future. Here, we will discuss recent strategies for the generation of cardiomyocytes from human embryonic stem cells and recapitulate their features, as well as highlight some in vitro applications for the cells. Finally, opportunities in the area of cardiac regenerative medicine will be illustrated.

摘要

在过去的十年中,人类胚胎干细胞能够自发分化为收缩性心肌细胞样细胞的能力引起了科学界的极大兴趣。从难以控制到现在,人类体外心肌发生正在成为一个可以在一定程度上进行有效操作和指导的过程。尽管仍有大量研究工作要做,但引导多能干细胞向心肌细胞谱系的新的和改进的方案正在科学文献中不断积累。然而,迄今为止描述的干细胞来源的心肌细胞通常类似于未成熟的胚胎/胎儿心肌细胞,并且在某些功能和结构方面与成年心肌细胞不同。因此,未来的挑战将是设计策略,最终可能使细胞在体外达到更高程度的成熟。尽管如此,使用当前方案可以制备的细胞仍然具有广泛的用途,并且它们已经开始进入制药行业使用的药物发现平台。此外,预计源自干细胞的心肌细胞和心肌祖细胞将对未来如何治疗心脏病产生巨大影响。在这里,我们将讨论从人类胚胎干细胞生成心肌细胞的最新策略,并概括其特征,以及强调细胞的一些体外应用。最后,将说明心脏再生医学领域的机会。

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