Maturation of Pluripotent Stem Cell-Derived Cardiomyocytes Enables Modeling of Human Hypertrophic Cardiomyopathy

Stem Cell Reports. 2021 Mar 9;16(3):519-533. doi: 10.1016/j.stemcr.2021.01.018. Epub 2021 Feb 25.


Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are a powerful platform for biomedical research. However, they are immature, which is a barrier to modeling adult-onset cardiovascular disease. Here, we sought to develop a simple method that could drive cultured hiPSC-CMs toward maturity across a number of phenotypes, with the aim of utilizing mature hiPSC-CMs to model human cardiovascular disease. hiPSC-CMs were cultured in fatty acid-based medium and plated on micropatterned surfaces. These cells display many characteristics of adult human cardiomyocytes, including elongated cell morphology, sarcomeric maturity, and increased myofibril contractile force. In addition, mature hiPSC-CMs develop pathological hypertrophy, with associated myofibril relaxation defects, in response to either a pro-hypertrophic agent or genetic mutations. The more mature hiPSC-CMs produced by these methods could serve as a useful in vitro platform for characterizing cardiovascular disease.

Keywords: HIF1α; cardiomyocyte maturation; disease modeling; hiPSC-CM; hiPSC-CM maturation; hypertrophic cardiomyopathy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cardiomyopathy, Hypertrophic / physiopathology*
  • Cell Culture Techniques / methods*
  • Cell Differentiation*
  • Cell Line
  • Cells, Cultured
  • Culture Media / chemistry
  • Fatty Acids / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • Induced Pluripotent Stem Cells / cytology
  • Induced Pluripotent Stem Cells / drug effects
  • Induced Pluripotent Stem Cells / physiology*
  • Models, Biological
  • Myocytes, Cardiac / cytology
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / physiology*
  • Myofibrils / physiology
  • Phenylephrine / pharmacology
  • Sarcomeres / physiology
  • Sequence Analysis, RNA
  • Signal Transduction


  • Culture Media
  • Fatty Acids
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Phenylephrine