Impelling force and current challenges by chemicals in somatic cell reprogramming and expansion beyond hepatocytes

Table 1 Expandable hepatic cells induced from primary hepatocytes to date

Hepatocyte source(s)	Chemicals	Growth factor(s)	Medium and supplements	Expansion potential		Yr
				Passage count	Doubling time
Mouse and Rat	A83-01, CHIR99021, Y-27632	EGF	DMEM/F12, HEPES, L-proline, ITS, dexamethasone, nicotinamide, ascorbic acid-2 phosphate, BSA, antibiotic/ antimycotic	Rat: >10; Mouse: >20	Rat: 14.7 ± 1.1 h	2017[62]
Mouse	A83-01, CHIR99021, Y-27632	EGF, HGF	DMEM/F12, N2 or ITS, S1P, LPA	>30	15-20 h	2017[63]
Human (resected patient liver tissue, non-lesion)	A83-01, CHIR99021	EGF, HGF	DMEM/F-12 (high glucose), FBS, nicotinamide, dexamethasone, ITS, penicillin/ streptomycin	>10	37.9-39.8 h	2018[64]
Human (resected patient liver tissue, non-lesion)	A83-01, CHIR99021, Y-27632	EGF, HGF	Advanced DMEM/F-12, N2, B27, sodium pyruvate, ascorbic acid, S1P, LPA	>10	24.7 ± 1.4 h	2018[67]
Human (normal, cryopreserved)	A83-01, Y-27632	EGF, FGF10, HGF, Wnt3a	Advanced DMEM/F-12, FBS, N2, B27 (minus vitamin A), N-acetylcysteine, nicotinamide, [Leu15]-gastrin I, penicillin/ streptomycin,	4 (normoxia); 8 (hypoxia)		2018[68]
Human (normal, freshly isolated and cryopreserved)	A83-01, CHIR99021, Y-27632	EGF, FGF7, FGF10, HGF, TGFa	Advanced DMEM/F-12, HEPES, B27 (minus vitamin A), R-spodin1 conditioned medium, N-acetylcysteine, nicotinamide, gastrin, GlutaMAX, penicillin/ streptomycin,	Fetal hepatocytes: >16	5-7 d	2018[70]