Enhancement of human iPSC-derived cardiomyocyte maturation by chemical conditioning in a 3D environment

Chen Yu Huang, Rebeca Peres Moreno Maia-Joca, Chin Siang Ong, Ijala Wilson, Deborah DiSilvestre, Gordon F. Tomaselli, Daniel H. Reich

Research output: Contribution to journalArticle

Abstract

Recent advances in the understanding and use of pluripotent stem cells have produced major changes in approaches to the diagnosis and treatment of human disease. An obstacle to the use of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) for regenerative medicine, disease modeling and drug discovery is their immature state relative to adult myocardium. We show the effects of a combination of biochemical factors, thyroid hormone, dexamethasone, and insulin-like growth factor-1 (TDI) on the maturation of hiPSC-CMs in 3D cardiac microtissues (CMTs) that recapitulate aspects of the native myocardium. Based on a comparison of the gene expression profiles and the structural, ultrastructural, and electrophysiological properties of hiPSC-CMs in monolayers and CMTs, and measurements of the mechanical and pharmacological properties of CMTs, we find that TDI treatment in a 3D tissue context yields a higher fidelity adult cardiac phenotype, including sarcoplasmic reticulum function and contractile properties consistent with promotion of the maturation of hiPSC derived cardiomyocytes.

Original languageEnglish (US)
Pages (from-to)1-11
Number of pages11
JournalJournal of Molecular and Cellular Cardiology
Volume138
DOIs
Publication statusPublished - Jan 2020
Externally publishedYes

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Keywords

  • 3D cardiac microtissues
  • Contractile function
  • Electrophysiology
  • Induced pluripotent stem cells
  • Maturation
  • TDI

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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