ArticleScientific reports2021
Physiological and pharmacological stimulation for in vitro maturation of substrate metabolism in human induced pluripotent stem cell-derived cardiomyocytes.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- Engineering the maturation of stem cell-derived cardiomyocytes.Frontiers in bioengineering and biotechnology · 2023Pooled it
- Article
- Article
- Metabolic Maturation in hiPSC-Derived Cardiomyocytes: Emerging Strategies for Inducing the Adult Cardiac Phenotype.Pharmaceuticals (Basel, Switzerland) · 2025Review
- FoxO1-zDHHC4-CD36 S-Acylation Axis Drives Metabolic Dysfunction in Diabetes.Circulation research · 2025Article
- Revitalizing the heart: strategies and tools for cardiomyocyte regeneration post-myocardial infarction.NPJ Regenerative medicine · 2025Review
- Article
- Advancing Cardiovascular Drug Screening Using Human Pluripotent Stem Cell-Derived Cardiomyocytes.International journal of molecular sciences · 2024Article
- Switching of hypertrophic signalling towards enhanced cardiomyocyte identity and maturity by a GATA4-targeted compound.Stem cell research & therapy · 2024Article
- FRESH™ 3D bioprinted cardiac tissue, a bioengineered platform forAPL bioengineering · 2023Article
- Metabolic Remodeling during Early Cardiac Lineage Specification of Pluripotent Stem Cells.Metabolites · 2023Article
- One Billion hiPSC-Cardiomyocytes: Upscaling Engineered Cardiac Tissues to Create High Cell Density Therapies for Clinical Translation in Heart Regeneration.Bioengineering (Basel, Switzerland) · 2023Article
- AKAP1 Regulates Mitochondrial Dynamics during the Fatty-Acid-Promoted Maturation of Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes as Indicated by Proteomics Sequencing.International journal of molecular sciences · 2023Article
- Research Progress towards the Effects of Fatty Acids on the Differentiation and Maturation of Human Induced Pluripotent Stem Cells into Cardiomyocytes.Reviews in cardiovascular medicine · 2023Review
- Development of appropriate fatty acid formulations to raise the contractility of constructed myocardial tissues.Regenerative therapy · 2022Article
- Differentiating Human Pluripotent Stem Cells to Cardiomyocytes Using Purified Extracellular Matrix Proteins.Bioengineering (Basel, Switzerland) · 2022Review
- Modelling Diabetic Cardiomyopathy: Using Human Stem Cell-Derived Cardiomyocytes to Complement Animal Models.Metabolites · 2022Review
- Time-regulated transcripts with the potential to modulate human pluripotent stem cell-derived cardiomyocyte differentiation.Stem cell research & therapy · 2022Article
- Characterization of cardiac metabolism in iPSC-derived cardiomyocytes: lessons from maturation and disease modeling.Stem cell research & therapy · 2022Review
- Guidelines on models of diabetic heart disease.American journal of physiology. Heart and circulatory physiology · 2022Review
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 4 countries.
Funding
Abstract
Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) enable human cardiac cells to be studied in vitro, although they use glucose as their primary metabolic substrate and do not recapitulate the properties of adult cardiomyocytes. Here, we have explored the interplay between maturation by stimulation of fatty acid oxidation and by culture in 3D. We have investigated substrate metabolism in hiPSC-CMs grown as a monolayer and in 3D, in porous collagen-derived scaffolds and in engineered heart tissue (EHT), by measuring rates of glycolysis and glucose and fatty acid oxidation (FAO), and changes in gene expression and mitochondrial oxygen consumption. FAO was stimulated by activation of peroxisome proliferator-activated receptor alpha (PPARα), using oleate and the agonist WY-14643, which induced an increase in FAO in monolayer hiPSC-CMs. hiPSC-CMs grown in 3D on collagen-derived scaffolds showed reduced glycolysis and increased FAO compared with monolayer cells. Activation of PPARα further increased FAO in cells on collagen/elastin scaffolds but not collagen or collagen/chondroitin-4-sulphate scaffolds. In EHT, FAO was significantly higher than in monolayer cells or those on static scaffolds and could be further increased by culture with oleate and WY-14643. In conclusion, a more mature metabolic phenotype can be induced by culture in 3D and FAO can be incremented by pharmacological stimulation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.