Effective cardiac myocyte differentiation of human induced pluripotent stem cells requires VEGF

PLoS One. 2013;8(1):e53764. doi: 10.1371/journal.pone.0053764. Epub 2013 Jan 10.

Abstract

Perhaps one of the most significant achievements in modern science is the discovery of human induced pluripotent stem cells (hiPSCs), which have paved the way for regeneration therapy using patients' own cells. Cardiomyocytes differentiated from hiPSCs (hiPSC-CMs) could be used for modelling patients with heart failure, for testing new drugs, and for cellular therapy in the future. However, the present cardiomyocyte differentiation protocols exhibit variable differentiation efficiency across different hiPSC lines, which inhibit the application of this technology significantly. Here, we demonstrate a novel myocyte differentiation protocol that can yield a significant, high percentage of cardiac myocyte differentiation (>85%) in 2 hiPSC lines, which makes the fabrication of a human cardiac muscle patch possible. The established hiPSCs cell lines being examined include the transgene integrated UCBiPS7 derived from cord blood cells and non-integrated PCBC16iPS from skin fibroblasts. The results indicate that hiPSC-CMs derived from established hiPSC lines respond to adrenergic or acetylcholine stimulation and beat regularly for greater than 60 days. This data also demonstrates that this novel differentiation protocol can efficiently generate hiPSC-CMs from iPSC lines that are derived not only from fibroblasts, but also from blood mononuclear cells.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Activins / pharmacology
  • Animals
  • Bone Morphogenetic Protein 4 / pharmacology
  • Cell Differentiation* / drug effects
  • Cell Differentiation* / genetics
  • Cell Line
  • Cell Lineage / drug effects
  • Coculture Techniques
  • Fetal Blood / cytology
  • Fetal Blood / drug effects
  • Fibroblasts / cytology
  • Gene Expression Regulation, Developmental / drug effects
  • Humans
  • Induced Pluripotent Stem Cells / cytology
  • Induced Pluripotent Stem Cells / metabolism
  • Leukocytes, Mononuclear* / cytology
  • Leukocytes, Mononuclear* / metabolism
  • Mice
  • Myocardium / cytology*
  • Myocytes, Cardiac / cytology*
  • Myocytes, Cardiac / drug effects
  • Vascular Endothelial Growth Factor A* / metabolism
  • Vascular Endothelial Growth Factor A* / pharmacology

Substances

  • BMP4 protein, human
  • Bone Morphogenetic Protein 4
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • activin A
  • Activins