Journal
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
Volume 15, Issue 1, Pages 38-51Publisher
WILEY
DOI: 10.1111/j.1582-4934.2009.00996.x
Keywords
induced pluripotent stem cells; cardiomyocytes; calcium transients; contractions; Beta adrenergic responsiveness; sarcoplasmic reticulum
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Funding
- Ministry of Science and Technology (MOST)
- Israel Science Foundation (ISF)
- Rappaport Family Institute for Research in the Medical Sciences
- Sohnis Family Stem Cells Center, the Russell Berrie Nanotechnology Institute, Technion
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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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