AMPK activator-treated human cardiac spheres enhance maturation and enable pathological modeling.
Stem Cell Res Ther
; 14(1): 322, 2023 11 08.
Article
em En
| MEDLINE
| ID: mdl-37941041
ABSTRACT
BACKGROUND:
Cardiac pathological outcome of metabolic remodeling is difficult to model using cardiomyocytes derived from human-induced pluripotent stem cells (hiPSC-CMs) due to low metabolic maturation.METHODS:
hiPSC-CM spheres were treated with AMP-activated protein kinase (AMPK) activators and examined for hiPSC-CM maturation features, molecular changes and the response to pathological stimuli.RESULTS:
Treatment of hiPSC-CMs with AMPK activators increased ATP content, mitochondrial membrane potential and content, mitochondrial DNA, mitochondrial function and fatty acid uptake, indicating increased metabolic maturation. Conversely, the knockdown of AMPK inhibited mitochondrial maturation of hiPSC-CMs. In addition, AMPK activator-treated hiPSC-CMs had improved structural development and functional features-including enhanced Ca2+ transient kinetics and increased contraction. Transcriptomic, proteomic and metabolomic profiling identified differential levels of expression of genes, proteins and metabolites associated with a molecular signature of mature cardiomyocytes in AMPK activator-treated hiPSC-CMs. In response to pathological stimuli, AMPK activator-treated hiPSC-CMs had increased glycolysis, and other pathological outcomes compared to untreated cells.CONCLUSION:
AMPK activator-treated cardiac spheres could serve as a valuable model to gain novel insights into cardiac diseases.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Proteínas Quinases Ativadas por AMP
/
Células-Tronco Pluripotentes Induzidas
Limite:
Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article