Molecular characterization and functional properties of cardiomyocytes derived from human inducible pluripotent stem cells

J Cell Mol Med. 2011 Jan;15(1):38-51. doi: 10.1111/j.1582-4934.2009.00996.x.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caffeine / pharmacology
  • Calcium / metabolism
  • Calsequestrin / genetics
  • Calsequestrin / metabolism
  • Cell Differentiation / drug effects
  • Cells, Cultured
  • Fibroblasts / metabolism
  • Fluorescent Antibody Technique
  • Foreskin / cytology
  • Gene Expression
  • Humans
  • Induced Pluripotent Stem Cells / cytology*
  • Kruppel-Like Factor 4
  • Kruppel-Like Transcription Factors / genetics
  • Male
  • Mice
  • Mice, SCID
  • Myocardial Contraction / drug effects
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / metabolism*
  • Octamer Transcription Factor-3 / genetics
  • Proto-Oncogene Proteins c-myc / genetics
  • RNA, Messenger / metabolism
  • Ryanodine / pharmacology
  • Ryanodine Receptor Calcium Release Channel / genetics
  • Ryanodine Receptor Calcium Release Channel / metabolism
  • SOXB1 Transcription Factors / genetics
  • Sarcoplasmic Reticulum / metabolism
  • Teratoma / metabolism
  • Teratoma / pathology

Substances

  • Calsequestrin
  • KLF4 protein, human
  • Klf4 protein, mouse
  • Kruppel-Like Factor 4
  • Kruppel-Like Transcription Factors
  • MYC protein, human
  • Octamer Transcription Factor-3
  • Proto-Oncogene Proteins c-myc
  • RNA, Messenger
  • Ryanodine Receptor Calcium Release Channel
  • SOX2 protein, human
  • SOXB1 Transcription Factors
  • Ryanodine
  • Caffeine
  • Calcium