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

Walter E. Knight, Yingqiong Cao, Ying Hsi Lin, Congwu Chi, Betty Bai, Genevieve C. Sparagna, Yuanbiao Zhao, Yanmei Du, Pilar Londono, Julie A. Reisz, Benjamin C. Brown, Matthew R.G. Taylor, Amrut V. Ambardekar, Joseph C. Cleveland, Timothy A. McKinsey, Mark Y. Jeong, Lori A. Walker, Kathleen C. Woulfe, Angelo D'Alessandro, Kathryn C. ChatfieldHongyan Xu, Michael R. Bristow, Peter M. Buttrick, Kunhua Song

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)519-533
Number of pages15
JournalStem Cell Reports
Volume16
Issue number3
DOIs
StatePublished - Mar 9 2021

Keywords

  • HIF1α
  • cardiomyocyte maturation
  • disease modeling
  • hiPSC-CM
  • hiPSC-CM maturation
  • hypertrophic cardiomyopathy

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

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