Table 2

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

Journal of Animal Reproduction and Biotechnology 2022;37:67-79 https://doi.org/10.12750/JARB.37.2.67