ryanodine and Teratoma

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.

Topics: Animals; Caffeine; Calcium; Calsequestrin; Cell Differentiation; Cells, Cultured; Fibroblasts; Fluorescent Antibody Technique; Foreskin; Gene Expression; Humans; Induced Pluripotent Stem Cells; Kruppel-Like Factor 4; Kruppel-Like Transcription Factors; Male; Mice; Mice, SCID; Myocardial Contraction; Myocytes, Cardiac; Octamer Transcription Factor-3; Proto-Oncogene Proteins c-myc; RNA, Messenger; Ryanodine; Ryanodine Receptor Calcium Release Channel; Sarcoplasmic Reticulum; SOXB1 Transcription Factors; Teratoma