Metabolic environment in vivo as a blueprint for differentiation and maturation of human stem cell-derived cardiomyocytes

Rolf H. Slaats, Verena Schwach, Robert Passier*

*Corresponding author for this work

Research output: Contribution to journalReview articleAcademicpeer-review

3 Citations (Scopus)
2 Downloads (Pure)

Abstract

Patient-derived human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) are increasingly being used for disease modeling, drug screening and regenerative medicine. However, to date, an immature, fetal-like, phenotype of hPSC-CMs restrains their full potential. Increasing evidence suggests that the metabolic state, particularly important for provision of sufficient energy in highly active contractile CMs and anabolic and regulatory processes, plays an important role in CM maturation, which affects crucial functional aspects of CMs, such as contractility and electrophysiology. During embryonic development the heart is subjected to metabolite concentrations that differ substantially from that of hPSC-derived cardiac cell cultures. A deeper understanding of the environmental and metabolic cues during embryonic heart development and how these change postnatally, will provide a framework for optimizing cell culture conditions and maturation of hPSC-CMs. Maturation of hPSC-CMs will improve the predictability of disease modeling, drug screening and drug safety assessment and broadens their applicability for personalized and regenerative medicine.

Original languageEnglish
Article number165881
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1866
Issue number10
DOIs
Publication statusPublished - 1 Oct 2020

Keywords

  • UT-Hybrid-D
  • Fatty acid
  • hPSC-cardiomyocytes
  • Maturation
  • Metabolism
  • Cardiac development

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