Development of regenerative cardiomyocytes from mesenchymal stem cells for cardiovascular tissue engineering
Development of regenerative cardiomyocytes from mesenchymal stem cells for cardiovascular tissue engineering
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DOI：
10.1046/j.1525-1594.2001.025003187.x
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发表时间：
2001-03-01
影响因子：
2.4
通讯作者：
Fukuda, K
中科院分区：
文献类型：
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作者：
Fukuda, K
我们从小鼠骨髓基质中分离出一株心肌细胞系。将基质细胞永生化，用5-氮胞苷处理，并反复筛选自发搏动细胞。细胞呈成纤维细胞样形态。经5-氮胞苷处理后，约30%的细胞形态发生改变，1周后与相邻细胞连接，2周后形成肌管样结构并开始自发搏动，3周后同步搏动。这些细胞表达心钠素(ANP)和脑利钠肽(BNP)。电子显微镜下可见心肌细胞样超微结构，包括典型的肌节和心房颗粒。均有窦房结或室壁细胞样动作电位。对肌球蛋白和α-肌动蛋白等收缩蛋白基因亚型的分析表明，它们的表型与胎儿心室肌细胞相似。这些细胞在5-氮胞苷处理前表达NKX2.5、GATA4、TEF-1和MEF2-C mRNA，处理后表达MEF2-A和MEF2-D。该新细胞系为心肌细胞移植的研究提供了有力的模型。
We have isolated a cardiomyogenic (CMG) cell line from murine bone marrow stroma. Stromal cells were immortalized, treated with 5-azacytidine, and spontaneous beating cells were repeatedly screened for. The cells showed a fibroblast-like morphology. However, this morphology changed after 5-azacytidine treatment in about 30% of the cells, which connected with adjoining cells after 1 week, formed myotube-like structures and began spontaneous beating after 2 weeks, and beat synchronously after 3 weeks. These cells expressed atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). Electron microscopy revealed a cardiomyocyte-like ultrastructure including typical sarcomeres and atrial granules. They had sinus node-like or ventricular cell-like action potentials. Analysis of the isoform of contractile protein genes, such as myosin and alpha -actin, indicated that their phenotype was similar to fetal ventricular cardiomyocytes. These cells expressed Nkx2.5, GATA4, TEF-1, and MEF2-C mRNA before 5-azacytidine treatment, and expressed MEF2-A and MEF2-D after treatment. This new cell line provides a powerful model for the study of cardiomyocyte transplantation.