Recent advances in regulating the proliferation or maturation of human-induced pluripotent stem cell-derived cardiomyocytes

Yang, Hao; Yang, Yuan; Kiskin, Fedir N.; Shen, Mengcheng; Zhang, Joe Z.

doi:10.1186/s13287-023-03470-w

Stem Cell Research & Therapy

Table 1 Summary of the effects of different methods on hiPSC-CM maturation and proliferation

From: Recent advances in regulating the proliferation or maturation of human-induced pluripotent stem cell-derived cardiomyocytes

Methods	Proliferation/Maturation	Effects	References
Cell cycle	Proliferation	Increase the number of Ki67, BrdU, pH3 and Aurora positive cells	[17, 18]
Small molecules	Proliferation	CHIR99021	[28, 29]
		Increased the number of Ki67 and pH3 positive cells
		Decreased contractile force
		Hit compounds from Hudson’s paper
		Increased the number of Ki67 and pH3 positive cells
Small molecules	Maturation	Fatty acid-based medium	[41, 51, 52]
		Increased contractile force
		Enhanced oxidative and glycolytic metabolism
		Enhanced calcium cycling
		Highly negative resting membrane potential and increased AP upstroke velocity
		T3 and glucocorticoids
		Larger cell size
		Improved myofibril organization
		T-tubule formation
		Increased contractile force
		Enhanced calcium handling
Prolonged culture	Maturation	Increased cell size	[7, 8]
		Increased number of MLC2v-positive/MLC2a-negative hiPSC-CMs
		No detection of T-tubules
Epigenetic regulation	Proliferation	miRNA	[64, 66, 83]
		Increased the number of Ki67, BrdU, pH3 and Aurora positive cells
		m6A modification
		Increased the number of EdU and pH3 positive cells
Epigenetic regulation	Maturation	miRNA	[68, 72]
		Larger cell size
		Increased contractile force
		Enhanced oxidative metabolism
		Histone modification
		Larger cell size
		Increased expression of genes related to ion channels
Co-culture	Proliferation	Increased the number of Ki67 positive cells	[87, 88]
Co-culture	Proliferation	Decreased sarcomere structural organization	[87, 88]
Co-culture	Maturation	Larger cell size	[93]
Co-culture	Maturation	Increased expression of genes related to ion channels	[93]
Substrate stiffness	Maturation	Improved myofibril organization	[97, 98, 101]
		Increased contractile force
		Enhanced oxidative metabolism
		Enhanced calcium handling
Physiological pattern	Maturation	Improved myofibril organization	[96, 105]
		T-tubule formation
		Increased contractile force
Conductivity	Maturation	Increased expression of genes related to ion channels	[108, 110]
Conductivity	Maturation	Enhanced calcium handling	[108, 110]
In vivo transplantation	Maturation	Larger cell size	[113, 114]
		Improved myofibril organization
		T-tubule formation
		Intercalated disc-like structure formation
		Increased contractile force
		Enhanced calcium handling
Electric stimulation	Maturation	Larger cell size	[125, 127]
		Improved myofibril organization
		Enhanced calcium handling
Mechanical stress	Maturation	Larger cell size	[138, 139]
		Improved myofibril organization
		Increased contractile force
Optogenetics	Maturation	Enhanced calcium handling	[133, 134]
Optogenetics	Maturation	Improved myofibril organization	[133, 134]
3D culture	Maturation	EHTs and spheroids	[118, 119, 146, 147]
		Larger cell size
		Improved myofibril organization
		T-tubule formation
		Intercalated disc-like structure formation
		Increased contractile force
		Enhanced calcium handling
		Enhanced oxidative metabolism
		Organoids
		Larger cell size
		Enhanced calcium handling
		Increased action potential amplitudes and upstroke velocity

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ISSN: 1757-6512

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