Generation of PDGFRα+ Cardioblasts from Pluripotent Stem Cells

Sci Rep. 2017 Feb 6:7:41840. doi: 10.1038/srep41840.

Abstract

Isolating actively proliferating cardioblasts is the first crucial step for cardiac regeneration through cell implantation. However, the origin and identity of putative cardioblasts are still unclear. Here, we uncover a novel class of cardiac lineage cells, PDGFRα+Flk1- cardioblasts (PCBs), from mouse and human pluripotent stem cells induced using CsAYTE, a combination of the small molecules Cyclosporin A, the rho-associated coiled-coil kinase inhibitor Y27632, the antioxidant Trolox, and the ALK5 inhibitor EW7197. This novel population of actively proliferating cells is cardiac lineage-committed but in a morphologically and functionally immature state compared to mature cardiomyocytes. Most important, most of CsAYTE-induced PCBs spontaneously differentiated into functional αMHC+ cardiomyocytes (M+CMs) and could be a potential cellular resource for cardiac regeneration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / pharmacology
  • Aniline Compounds / pharmacology
  • Animals
  • Antioxidants / pharmacology
  • Cell Differentiation*
  • Cell Line
  • Cells, Cultured
  • Chromans / pharmacology
  • Cyclosporine / pharmacology
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Mice
  • Myoblasts / cytology*
  • Myoblasts / metabolism
  • Myocytes, Cardiac / cytology*
  • Myocytes, Cardiac / metabolism
  • Pluripotent Stem Cells / cytology*
  • Pluripotent Stem Cells / drug effects
  • Pluripotent Stem Cells / metabolism
  • Pyridines / pharmacology
  • Receptor, Platelet-Derived Growth Factor alpha / genetics
  • Receptor, Platelet-Derived Growth Factor alpha / metabolism*
  • Triazoles / pharmacology

Substances

  • Amides
  • Aniline Compounds
  • Antioxidants
  • Chromans
  • Enzyme Inhibitors
  • Pyridines
  • Triazoles
  • Y 27632
  • vactosertib
  • Cyclosporine
  • Receptor, Platelet-Derived Growth Factor alpha
  • 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid