Table 5.
Cardiac Cell Maturation Components
| Classification | Maturation component | Description |
|---|---|---|
| Culture supplement | B27 | B27 is a media supplement containing various hormones, lipids, and amino acids that promotes iPSC-CM maintenance and maturation.269 |
| Insulin | Insulin supports the growth and metabolism of myocardial cells.270 | |
| Hormone | Thyroid hormone (T3) | T3 increases contractile force, calcium release and reuptake, and cardiomyocyte size.155–157,271 |
| Dexamethasone | Dexamethasone, which is a glucocorticoid which enhances electromechanical maturation of iPSC-derived cardiomyocytes.152 | |
| Growth factor | IGF-1 | IGF-1 regulates contractility, metabolism, hypertrophy, and apoptosis in the heart.155 |
| Fatty acids | Oleic acid | Fatty acids improve contractile force, metabolism, and function of cardiac cells.163,271–273 |
| Palmitic acid/palmitate | ||
| Linoleic acid | ||
| Sodium L-lactate | ||
| Small molecules | Phosphodiesterase inhibitor (IBMX) | The addition of IBMX increases contractile activity and force.160,161 |
| HIF-1α inhibitor (FM19G1) | Increases fatty acid oxidation.272 | |
| PPARα agonist (WY-14643) | Facilitates mitochondrial metabolic maturation.272 | |
| mTOR inhibitor (Torin1) | Facilitates cardiomyocyte quiescence.274 | |
| Monosaccharide | Galactose | Addition of galactose to maturation media improves maturation speed and total oxidative capacity.271 |
| Amino acids | Taurine | Taurine is used for fat absorption, cardiomyocyte energetics, and as a pH buffer in the mitochondrial matrix for stabilization.152,275 |
| L-glutamine | L-glutamine promotes increased beating function and decreased apoptosis of cardiomyocytes.276 | |
| L-carnitine | Carnitine assists in transport of fatty acids through the mitochondrial membrane.163,277 | |
| Creatine | Creatine is an important temporal and spatial energy source.275,277 | |
| Genetic manipulation | Let-7 | Let-7 enhances cardiomyocyte size, sarcomere length, contraction force, and respiratory capacity.278 |
| microRNA-1 | miR-1 assists in facilitation of electrophysiological maturation.158,279 | |
| microRNA-499 | miR-499 promotes ventricular specification of human embryonic stem cells.158,279 | |
| Micropatterning | Sarcomeric alignment | Cardiomyocyte sarcomeric alignment and formation are improved after plated onto micropatterned matrices.22,280–283 |
IGF-1, insulin-like growth factor 1.