Heparin Promotes Cardiac Differentiation of Human Pluripotent Stem Cells in Chemically Defined Albumin-Free Medium, Enabling Consistent Manufacture of Cardiomyocytes

Stem Cells Transl Med. 2017 Feb;6(2):527-538. doi: 10.5966/sctm.2015-0428. Epub 2016 Sep 2.

Abstract

Cardiomyocytes can be differentiated from human pluripotent stem cells (hPSCs) in defined conditions, but efficient and consistent cardiomyocyte differentiation often requires expensive reagents such as B27 supplement or recombinant albumin. Using a chemically defined albumin-free (E8 basal) medium, we identified heparin as a novel factor that significantly promotes cardiomyocyte differentiation efficiency, and developed an efficient method to differentiate hPSCs into cardiomyocytes. The treatment with heparin helped cardiomyocyte differentiation consistently reach at least 80% purity (up to 95%) from more than 10 different hPSC lines in chemically defined Dulbecco's modified Eagle's medium/F-12-based medium on either Matrigel or defined matrices like vitronectin and Synthemax. One of heparin's main functions was to act as a Wnt modulator that helped promote robust and consistent cardiomyocyte production. Our study provides an efficient, reliable, and cost-effective method for cardiomyocyte derivation from hPSCs that can be used for potential large-scale drug screening, disease modeling, and future cellular therapies. Stem Cells Translational Medicine 2017;6:527-538.

Keywords: Cardiac; Cell culture; Embryonic stem cells; Heparin; Induced pluripotent stem cells.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't
  • Video-Audio Media

MeSH terms

  • Cell Culture Techniques
  • Cell Differentiation / drug effects*
  • Cell Line
  • Cell Proliferation / drug effects*
  • Culture Media / chemistry*
  • Heparin / pharmacology*
  • Human Embryonic Stem Cells / drug effects*
  • Human Embryonic Stem Cells / metabolism
  • Humans
  • Induced Pluripotent Stem Cells / drug effects*
  • Induced Pluripotent Stem Cells / metabolism
  • Myocytes, Cardiac / drug effects*
  • Myocytes, Cardiac / metabolism
  • Phenotype
  • Time Factors
  • Wnt Signaling Pathway / drug effects

Substances

  • Culture Media
  • Heparin