Flk1+cardiac stem/progenitor cells derived from embryonic stem cells improve cardiac function in a dilated cardiomyopathy mouse model
Flk1+cardiac stem/progenitor cells derived from embryonic stem cells improve cardiac function in a dilated cardiomyopathy mouse model
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Flk1+源自胚胎干细胞的心脏干/祖细胞改善扩张型心肌病小鼠模型的心脏功能
DOI：
10.1016/j.cardiores.2007.05.013
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发表时间：
2007-10-01
影响因子：
10.8
通讯作者：
Nakahata, Tatsutoshi
中科院分区：
文献类型：
--
作者：
Baba, Shiro;Heike, Toshio;Nakahata, Tatsutoshi
目的：来自胚胎干细胞（ES）的Flk1（+）细胞可以分化为中胚层细胞，如造血细胞和内皮细胞。在这里，我们证明它们可以在扩张型心肌病（DCM） C57/BL6小鼠模型中发育成支持功能恢复的心肌细胞。方法：分化第4天对Flk1（+）和Flk1（-）细胞进行分选，体外观察心肌发生情况。接下来，我们将这些细胞移植到心肌病小鼠的心脏中，以评估心功能的改善。结果：分化后第4天分离的Flk1（+）细胞可有效转化为收缩性心肌细胞，而非Flk1（-）细胞。RT-PCR分析和免疫组织学分析表明，Flk1（+）细胞衍生的收缩细胞在分化后第10天体外表达成熟的心脏标志物。通过超声心动图和心导管检查发现，将Flk1（+）细胞移植到DCM模型小鼠心脏中可改善心功能。免疫组化证实，体内分化的Flk1+细胞表达心脏标记物并具有间隙连接。此外，这些细胞产生类似于成人心室的心室型动作电位。结论：Flk1在体外和体内均可分化为成熟心肌细胞，是鉴别心脏干/祖细胞的良好标记物。(C) 2007年欧洲心脏病学会。Elsevier B.V.版权所有。
Objectives: Flk1(+) cells derived from embryonic stem (ES) cells are known to differentiate into mesodermal lineages such as hematopoietic and endothelial cells. Here we demonstrate that they can develop into cardiomyocytes that support functional recovery in a dilated cardiomyopathy (DCM) C57/BL6 mouse model.Methods: Flk1(+) and Flk1(-) cells were sorted at day 4 of differentiation, and cardiomyogenesis was assessed in vitro. Next, we transplanted these cells into the hearts of cardiomyopathy mice to assess improvement in cardiac function.Results: Flk1(+) cells, but not Flk1(-) cells, isolated on day 4 after differentiation were efficiently converted into contractile cardiomyocytes. RT-PCR analysis and immunohistological assays demonstrated that contractile cells derived from Flk1(+) cells in vitro expressed mature cardiac markers on day 10 after differentiation. Transplantation of sorted Flk1(+) cells into DCM model mouse hearts improved cardiac function, as determined by echocardiography and cardiac catheterization. The in vivo differentiated Flk1+ cells expressed cardiac markers and had gap junctions, as demonstrated by immunchistochemistry. Furthermore, these cells generated ventricular type action potentials similar to those of adult ventricle.Conclusion: These results indicate that Flk1 is a good marker for sorting cardiac stem/progenitor cells which can differentiate into mature cardiomyocytes both in vitro and in vivo. (C) 2007 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.