Neural Crest–Derived Stem Cells Migrate and Differentiate Into Cardiomyocytes After Myocardial Infarction
Neural Crest–Derived Stem Cells Migrate and Differentiate Into Cardiomyocytes After Myocardial Infarction
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DOI：
10.1161/atvbaha.110.214726
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发表时间：
2011-03
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影响因子：
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通讯作者：
Yuichi Tamura;Keisuke Matsumura;M. Sano;H. Tabata;Kensuke Kimura;M. Ieda;Takahide Arai;Yohei Ohno;H. Kanazawa;S. Yuasa;R. Kaneda;S. Makino;K. Nakajima;H. Okano;K. Fukuda
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文献类型：
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作者：
Yuichi Tamura;Keisuke Matsumura;M. Sano;H. Tabata;Kensuke Kimura;M. Ieda;Takahide Arai;Yohei Ohno;H. Kanazawa;S. Yuasa;R. Kaneda;S. Makino;K. Nakajima;H. Okano;K. Fukuda
我们最近证明，原始神经嵴衍生（NC）细胞在胚胎发育期间从心脏神经嵴迁移，并作为休眠干细胞留在心脏中，具有分化为各种细胞类型的能力，包括心肌细胞。在这里，我们研究了这些细胞在心肌梗死（MI）的迁移和分化潜力。方法和结果-我们通过将蛋白0启动子Cre小鼠与Floxed增强型绿色荧光蛋白小鼠杂交获得双转基因小鼠，其中NC细胞表达增强型绿色荧光蛋白。在新生儿心脏中，NC干细胞（NCSC）主要位于流出道，但它们也以梯度从基部到心尖分布在整个心室肌中。延时录像分析显示，非国家家庭佣工是移徙性的。一些NCSC在成人心脏中持续存在。在MI时，NCSC聚集在缺血边界区（BZA），表达单核细胞趋化蛋白-1（MCP-1）。离体细胞迁移试验表明，MCP-1诱导NCSC迁移，这种趋化作用显着抑制抗MCP-1抗体。MI后2周，小NC心肌细胞首次出现在BZA中，此后数量逐渐增加。结论-这些结果表明，NCSC迁移到BZA通过MCP-1/CCR 2信号转导，并有助于心肌梗死后心脏再生的心肌细胞的供应。
Objective—We recently demonstrated that primitive neural crest–derived (NC) cells migrate from the cardiac neural crest during embryonic development and remain in the heart as dormant stem cells, with the capacity to differentiate into various cell types, including cardiomyocytes. Here, we examined the migration and differentiation potential of these cells on myocardial infarction (MI). Methods and Results—We obtained double-transgenic mice by crossing protein-0 promoter-Cre mice with Floxed–enhanced green fluorescent protein mice, in which the NC cells express enhanced green fluorescent protein. In the neonatal heart, NC stem cells (NCSCs) were localized predominantly in the outflow tract, but they were also distributed in a gradient from base to apex throughout the ventricular myocardium. Time-lapse video analysis revealed that the NCSCs were migratory. Some NCSCs persisted in the adult heart. On MI, NCSCs accumulated at the ischemic border zone area (BZA), which expresses monocyte chemoattractant protein-1 (MCP-1). Ex vivo cell migration assays demonstrated that MCP-1 induced NCSC migration and that this chemotactic effect was significantly depressed by an anti-MCP-1 antibody. Small NC cardiomyocytes first appeared in the BZA 2 weeks post-MI and gradually increased in number thereafter. Conclusion—These results suggested that NCSCs migrate into the BZA via MCP-1/CCR2 signaling and contribute to the provision of cardiomyocytes for cardiac regeneration after MI.