Mitochondrial Maturation in Human Pluripotent Stem Cell Derived Cardiomyocytes.
Mitochondrial Maturation in Human Pluripotent Stem Cell Derived Cardiomyocytes.
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DOI：
10.1155/2017/5153625
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发表时间：
2017
影响因子：
4.3
通讯作者：
Tian R
中科院分区：
文献类型：
--
作者：
Dai DF;Danoviz ME;Wiczer B;Laflamme MA;Tian R
人多能干细胞来源的心肌细胞（PSC-CMs）已被广泛用于疾病建模、药物安全性筛选和临床前细胞治疗以再生心肌。大多数研究利用分化后相对较短时间内体外培养的PSC-CM。这些PSC-CMs显示了原始心肌细胞的结构、电生理和机械特征。一些研究延长了PSC-CM体外培养时间，并报道了结构和机电性能成熟的改善。然而，线粒体成熟的程度仍不清楚。本研究描述了线粒体在长时间体外培养过程中的发育。随着培养时间的延长，PSC-CM表现出线粒体成熟的改善，线粒体相对丰度增加，膜电位增强，几个线粒体呼吸复合物的活性增加。这些与其他细胞成分的成熟是平行的。然而，与人胎心在相同时间间隔内观察到的线粒体成熟相比，体外培养的PSC-CMs中的线粒体成熟表现出不理想的成熟。
Human pluripotent stem cells derived cardiomyocytes (PSC-CMs) have been widely used for disease modeling, drug safety screening, and preclinical cell therapy to regenerate myocardium. Most studies have utilized PSC-CM grown in vitro for a relatively short period after differentiation. These PSC-CMs demonstrated structural, electrophysiological, and mechanical features of primitive cardiomyocytes. A few studies have extended in vitro PSC-CM culture time and reported improved maturation of structural and electromechanical properties. The degree of mitochondrial maturation, however, remains unclear. This study characterized the development of mitochondria during prolonged in vitro culture. PSC-CM demonstrated an improved mitochondrial maturation with prolonged culture, in terms of increased mitochondrial relative abundance, enhanced membrane potential, and increased activity of several mitochondrial respiratory complexes. These are in parallel with the maturation of other cellular components. However, the maturation of mitochondria in PSC-CMs grown for extended in vitro culture exhibits suboptimal maturation when compared with the maturation of mitochondria observed in the human fetal heart during similar time interval.