Cell Reports (May 2024)

Independent compartmentalization of functional, metabolic, and transcriptional maturation of hiPSC-derived cardiomyocytes

  • K. Ashley Fetterman,
  • Malorie Blancard,
  • Davi M. Lyra-Leite,
  • Carlos G. Vanoye,
  • Hananeh Fonoudi,
  • Mariam Jouni,
  • Jean-Marc L. DeKeyser,
  • Brian Lenny,
  • Yadav Sapkota,
  • Alfred L. George, Jr.,
  • Paul W. Burridge

Journal volume & issue
Vol. 43, no. 5
p. 114160

Abstract

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Summary: Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) recapitulate numerous disease and drug response phenotypes, but cell immaturity may limit their accuracy and fidelity as a model system. Cell culture medium modification is a common method for enhancing maturation, yet prior studies have used complex media with little understanding of individual component contribution, which may compromise long-term hiPSC-CM viability. Here, we developed high-throughput methods to measure hiPSC-CM maturation, determined factors that enhanced viability, and then systematically assessed the contribution of individual maturation medium components. We developed a medium that is compatible with extended culture. We discovered that hiPSC-CM maturation can be sub-specified into electrophysiological/EC coupling, metabolism, and gene expression and that induction of these attributes is largely independent. In this work, we establish a defined baseline for future studies of cardiomyocyte maturation. Furthermore, we provide a selection of medium formulae, optimized for distinct applications and priorities, that promote measurable attributes of maturation.

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