The Sohnis Family Stem Cells Center, Technion - Israel Institute of Technology, Haifa, Israel.
J Cell Mol Med. 2011 Jan;15(1):38-51. doi: 10.1111/j.1582-4934.2009.00996.x.
In view of the therapeutic potential of cardiomyocytes derived from induced pluripotent stem (iPS) cells (iPS-derived cardiomyocytes), in the present study we investigated in iPS-derived cardiomyocytes, the functional properties related to Ca(2+) handling and contraction, the contribution of the sarcoplasmic reticulum (SR) Ca(2+) release to contraction and the b-adrenergic inotropic responsiveness. The two iPS clones investigated here were generated through infection of human foreskin fibroblasts (HFF) with retroviruses containing the four human genes: OCT4, Sox2, Klf4 and C-Myc. Our major findings showed that iPS-derived cardiomyocytes: (i) express cardiac specific RNA and proteins; (ii) exhibit negative force-frequency relations and mild (compared to adult) post-rest potentiation; (iii) respond to ryanodine and caffeine, albeit less than adult cardiomyocytes, and express the SR-Ca(2+) handling proteins ryanodine receptor and calsequestrin. Hence, this study demonstrates that in our cardiomyocytes clones differentiated from HFF-derived iPS, the functional properties related to excitation-contraction coupling, resemble in part those of adult cardiomyocytes.
鉴于诱导多能干细胞（iPS）衍生的心肌细胞（iPS 衍生的心肌细胞）的治疗潜力，本研究在 iPS 衍生的心肌细胞中研究了与 Ca(2+) 处理和收缩相关的功能特性、肌浆网（SR）Ca(2+)释放对收缩的贡献以及 b-肾上腺素能变力反应性。本研究中研究的这两个 iPS 克隆是通过将含有四个人类基因的逆转录病毒感染人包皮成纤维细胞（HFF）而产生的：OCT4、Sox2、Klf4 和 C-Myc。我们的主要发现表明，iPS 衍生的心肌细胞：（i）表达心脏特异性 RNA 和蛋白质；（ii）表现出负力频率关系和轻度（与成年相比）后休息增强；（iii）对 Ryanodine 和咖啡因有反应，尽管不如成年心肌细胞，但表达 SR-Ca(2+)处理蛋白 Ryanodine 受体和 Calsequestrin。因此，这项研究表明，在我们从 HFF 衍生的 iPS 分化而来的心肌细胞克隆中，与兴奋-收缩偶联相关的功能特性部分类似于成年心肌细胞的特性。
