pISSN: 2671-4639
eISSN: 2671-4663
Clinical trials with hPSC-derived CPCs or cardiomyocytes
Characteristics | Category | Cardiomyocytes | References | |
---|---|---|---|---|
Immature (Fetal or PSC-derived) | Mature | |||
Morphology | Shape | Circular and oblong | Anisotropic rod-like | Lundy et al., 2013 |
Size | Diameters: 5-10 μm Heights: ~5 μm Length: 30 μm Width: 10 μm Volume: 2,000 μm3 |
Heights: 15 μm Length: 150 μm Width: 20 μm Volume: 40,000 μm3 |
Bulatovic et al., 2016 Lundy et al., 2013 |
|
Nucleus | Mononucleated diploid | Multinucleated tetraploid | Denning et al., 2016 | |
Structure (Cytoskeleton) | Sarcomere: disorganized, short SR and T-tubule: poorly developed |
Sarcomere: highly organized, long SR and T-tubule: well-developed |
Denning et al., 2016 Yang et al., 2014a |
|
Electrophysiology | Beating | Spontaneously beat Force: 0.08-4 mN/mm2 mixed action potential (nodal, atrial ventricular-like) |
Start: Sinoatrial node No beat until triggered by the depolarization form adjacent cells Force: 40-80 mN/mm2 |
Lin et al., 2017 |
Resting membrane potential | -60 mV, nodal like | -90 mV | Koivumäki et al., 2018 | |
Conduction velocity | 10-20 cm/s | Around 60 cm/s | Denning et al., 2016 | |
Upstroke velocity | Slow, 10-50 V/s | Fast, 150-350 V/s | Denning et al., 2016 Veerman et al., 2017 |
|
Repolarization | Fast | Slow, after plateau phase | Jeevaratnam et al., 2018 Zhao et al., 2018 |
|
Channel protein | INa, ICa-L, Ito Low IK1, |
INa, ICa-L, Ito, IKr, IKs | Goversen et al., 2018 | |
Calcium handling | 1) Similar expression of Na+/Ca2+ exchanger with adult CMs 2) Low Expression of other Ca2+ releasing related protein 3) Increasing of calcium stores in the SR 4) Slower calcium dynamics with delayed time to peak and slower decay of the calcium signal |
Depolarization → opening of LTCC → calcium influx → calcium-induced calcium releasing → sliding of myofilament and contraction of muscle Calcium releasing: 1) SERCA2a 2) Sarcolemmal Na+/Ca2+ exchanger 3) Sarcolemmal Ca2+-ATPase 4) Mitochondrial Ca2+ uniport |
Hwang et al., 2015 Karakikes et al., 2015 Youm, 2016 Eisner et al., 2017 |
|
Metabolism | Mitochondria | Location: perinuclear space Low number and small size (<5% of total cell volume) Round shape and low cristae density In mouse, opened mitochondrial permeability transition (MPT) not induce cytochrome c leakage or apoptosis |
Location: between myofibrils and under the sarcolemma increase in both size and number (~30% of total cell volume) Oval shape and dense cristae → sufficient surface area |
Feric and Radisic, 2016 |
Energy source | Energy was generated mainly by glycolysis(Low fatty acid/ High glucose or lactate) Approximately 15% of total energy consumption in fetal cardiomyocytes is supplied with β-oxidation of fatty acids |
Approximately 80% of total energy consumption in adult cardiomyocytes is supplied with β-oxidation of fatty acids 60-70% ATP for contractile function, followed SERCA and of other ion transporters |
Correia et al., 2017 Galdos et al., 2017 Karakikes et al., 2015 Piquereau et al., 2018 |
|
Gene expression | Sarcomeric gene (MHC) | α-MHC | β-MHC | Katrukha, 2013 Lundy et al., 2013 |
Troponin I | TNNI1 | TNNI3 | Katrukha, 2013 | |
Others | Low expression levels of SERCA2, Caveolin 3, KCNH2 etc. | Lundy et al., 2013 |