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

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1866

Review

Slaats, Rolf H.¹  Schwach, Verena¹  Passier, Robert^1,2 

[1] Univ Twente, TechMed Ctr, Dept Appl Stem Cell Technol, Drienerlolaan 5, NL-7500 AE Enschede, Netherlands

[2] Leiden Univ, Dept Anat & Embryol, Med Ctr, POB 9600, NL-2300 RC Leiden, Netherlands

关键词: Metabolism;    Maturation;    hPSC-cardiomyocytes;    Cardiac development;    Fatty acid;   

DOI  :  10.1016/j.bbadis.2020.165881

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

Free