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

• Published in: Biochimica et biophysica acta. Molecular basis of disease 2020-10, Vol.1866 (10), p.165881, Article 165881
• Main Authors: Slaats, Rolf H., Schwach, Verena, Passier, Robert
• Format: Article
• Language: English
• Subjects: Cardiac development; Cell Differentiation; Cells, Cultured; Drug Evaluation, Preclinical - methods; Fatty acid; Heart - embryology; hPSC-cardiomyocytes; Humans; Maturation; Metabolism; Myocardial Contraction; Myocardium - cytology; Myocardium - metabolism; Myocytes, Cardiac - metabolism; Pluripotent Stem Cells - metabolism; Primary Cell Culture; Regenerative Medicine - methods; Toxicity Tests - methods
• ISSN: 0925-4439; 1879-260X
• DOI: 10.1016/j.bbadis.2020.165881

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. [Display omitted] •hPSC-CMs are characterized by metabolic and functional immaturity.•Metabolism influences maturation of CMs in vivo and in vitro.•The metabolic micro-environment in vitro differs substantially from in vivo.•Reformulation of culture medium may enable enhanced maturation of hPSC-CMs in vitro.