High-resolution electrophysiological assessment of human embryonic stem cell-derived cardiomyocytes - A novel in vitro model for the study of conduction
High-resolution electrophysiological assessment of human embryonic stem cell-derived cardiomyocytes - A novel in vitro model for the study of conduction
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DOI：
10.1161/01.res.0000039084.30342.9b
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发表时间：
2002-10-18
影响因子：
20.1
通讯作者：
Gepstein, L
中科院分区：
文献类型：
--
作者：
Kehat, I;Gepstein, A;Gepstein, L
本报告的目的是建立一种新的体外模型，用于研究脉冲在人体心脏组织中的传播。通过使用人胚胎干细胞分化系统，在三维分化细胞聚集体（胚状体）中产生自发收缩区域。形态学分析显示早期心脏表型的各向同性组织。缝隙连接，通过免疫染色的connexin 43和connexin 45评估，分布沿着细胞边界。高分辨率激活图显示存在功能性合胞体，具有稳定的局灶性激活和传导特性。与广泛的心肌细胞区域相比，狭窄的收缩组织中的传导明显较慢。这种独特的体外人体模型的建立可用于评估长期的结构-功能关系，用于药理学研究，用于组织工程，并可允许遗传修饰的心肌细胞的研究。
The goal of the present report was to establish a new in vitro model for the study of impulse propagation in human cardiac tissue. By using the human embryonic stem cell differentiating system, spontaneously contracting areas were generated in three-dimensional differentiating cell aggregates (embryoid bodies). Morphological analysis revealed an isotropic tissue of early-stage cardiac phenotype. Gap junctions, assessed by immunostaining of connexin43 and connexin45, were distributed along the cell borders. High-resolution activation maps demonstrated the presence of a functional syncytium with stable focal activation and conduction properties. Conduction was significantly slower in narrow bands of contracting tissue compared with broad cardiomyocyte regions. Establishment of this unique in vitro human model may be used for the assessment of long-term structure-function relationships, for pharmacological studies, for tissue engineering, and may permit the study of genetically modified cardiomyocytes.