Molecular characterization and functional properties of cardiomyocytes derived from human inducible pluripotent stem cells |
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| Authors: | Anna Ziskind Sivan Eliyahu Gideon Meiry Michal Amit Joseph Itskovitz‐Eldor Ofer Binah |
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| Institution: | 1. The Sohnis Family Stem Cells Center, Technion – Israel Institute of Technology, Haifa, Israel;2. Ruth & Bruce Rappaport Faculty of Medicine, Technion – Israel Institute of Technology, Haifa, Israel;3. The Rappaport Family Institute for Research in the Medical Sciences, Technion – Israel Institute of Technology, Haifa, Israel;4. Rambam Medical Center, Haifa, Israel |
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| Abstract: | 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 Ca2+]i handling and contraction, the contribution of the sarcoplasmic reticulum (SR) Ca2+ 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‐Ca2+ 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. |
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| Keywords: | induced pluripotent stem cells cardiomyocytes calcium transients contractions Beta adrenergic responsiveness sarcoplasmic reticulum |
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