title: Molecular characterization and functional properties of cardiomyocytes derived from human inducible pluripotent stem cells.
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 [Ca(2+) ](i) 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.
authors.affiliation: The Sohnis Family Stem Cells Center, Technion - Israel Institute of Technology, Haifa, Israel.
authors.forename: Igal
authors.initials: I
authors.lastname: Germanguz
authors.forename: Oshra
authors.initials: O
authors.lastname: Sedan
authors.forename: Naama
authors.initials: N
authors.lastname: Zeevi-Levin
authors.forename: Ronit
authors.initials: R
authors.lastname: Shtrichman
authors.forename: Efrat
authors.initials: E
authors.lastname: Barak
authors.forename: Anna
authors.initials: A
authors.lastname: Ziskind
authors.forename: Sivan
authors.initials: S
authors.lastname: Eliyahu
authors.forename: Gideon
authors.initials: G
authors.lastname: Meiry
authors.forename: Michal
authors.initials: M
authors.lastname: Amit
authors.forename: Joseph
authors.initials: J
authors.lastname: Itskovitz-Eldor
authors.forename: Ofer
authors.initials: O
authors.lastname: Binah
mesh_terms: D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002155:Calsequestrin / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D052816:Foreskin / Q000166:cytology; D015870:Gene Expression; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009200:Myocardial Contraction / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D050814:Octamer Transcription Factor-3 / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D012433:Ryanodine / Q000494:pharmacology; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000235:genetics; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D013724:Teratoma / Q000378:metabolism / Q000473:pathology
chemical_list: D002155:Calsequestrin; C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; C489427:MYC protein, human; D050814:Octamer Transcription Factor-3; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D019837:Ryanodine Receptor Calcium Release Channel; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D012433:Ryanodine; D002110:Caffeine; D002118:Calcium