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Table 1 Comparison of potential cell sources for cell-based treatment of liver failure

From: Generation of functional human hepatocytes in vitro: current status and future prospects

  Cell source Methods Features CYP positivity and activity in vitro Animal model Repopulation efficiency Serum human ALB concentration Ref.
DE cells iPSCs Activin A Prolonged survival NSG mice treated with DMN (chronic liver injury) 13–35% [4]
ICGhigh HL cells ESCs Lithium, OSM, DEX, and HGF Gamma-glutamyl transpeptidase activity, glycogen accumulation, and urea secretion Expression of CYP1A2 and CYP3A4 BALB/c nude mice treated with CCl4 (acute liver injury) 10.2 ± 3.11% at 7 weeks 3 μg/ml at 7 weeks [5]
iPSC-LBs iPSCs Coculture with endothelial and mesenchymal cells Early hepatic marker positive and connections between human and host vessels Expression of CYP3A7 TK-NOG mice 1.7 μg/ml at 6 weeks [6]
HL cells ESCs/iPSCs Activin A, FGF, HGF, and DEX LDL uptake, lipid storage, glycogen storage, and uptake and excretion of ICG Expression of CYP3A4 MUP-uPA/SCID/Bg mice 1–20% at 100 days 0.1–6.4 mg/ml at 100 days [7]
iMPC-Heps Fibroblasts OCT4, SOX2, KLF4, CHIR99021, DLPC, NaB, Par, RG, Activin A, bFGF, EGF, A83-01, BMP4, DEX, HGF, OSM, and Compound E Hepatocyte marker positive Activities of CYP3A4 and CYP2C19 FRG mice 2% at 9 months 100 μg/ml at ~ 35 weeks [8]
iHeps Fibroblasts HNF6, HNF4α, HNF1α, CEBPA, PROX1, and ATF5 Glycogen synthesis, LDL uptake, exclusion of absorbed ICG, and accumulation of fatty droplets Activities of CYP3A4, CYP1A2, and CYP2B6 Tet-uPA/Rag2−/−/γc−/− mice 30% at 7 weeks 150 μg/mL at 7 weeks [9]
iHeps/iHepsLT Fibroblasts FOXA3, HNF1β, and HNF4α (SV40) Hepatocyte marker positive, glycogen storage, ICG absorption, acetylated LDL uptake, and cytoplasmic accumulation of triglycerides and lipids Activities of CYP1A2, CYP2A, and CYP2D6 F/R mice 0.3–4.2% at 9 weeks 350 ng/ml at 9 weeks [10]
hiEndoPC-Heps Gastric epithelial cells Bay, Bix, RG, SB, BMP4, Wnt3a, FGF4, HGF, DEX, and OSM Uptake of ICG and LDL, glycogen storage, and accumulation of fatty droplets CYP3A4 activity F/R mice 10% at 8–10 weeks 350 ng/ml at 8 weeks [11]
CFPHs Hepatocytes Long-term culture Liver progenitor cell marker positive Expression of CYP2C9, CYP2C19, CYP1A1, and CYP1A2 uPA/SCID mice 0.2–27.0% at 9–10 weeks 9–728 μg/mL at 9–10 weeks [12, 13]
Human liver organoid Ductal cells (EPCAM+) N2, B27, N-acetylcysteine, gastrin, EGF, R-spondin1, FGF10, HGF, nicotinamide, A83-01, and FSK Hepatocyte morphology,
glycogen accumulation, and LDL uptake
CYP3A4 activity BALB/c nude mice treated with CCl4 (acute liver injury) 80 ng/ml at 6 weeks [14]
hCdHs Hepatocytes HGF, A83-01, and CHIR99021 High nucleus-to-cytoplasm ratio, pluripotency stem cell marker positive, and hepatic progenitor cell marker expression CYP1A2 activity Alb-TRECK/SCID mice 1.5 μg/ml [15]
HepLPCs Hepatocytes N2, B27, HGF, EGF, Y27632, A83-01, CHIR99021, S1P, and LPA High nucleus-to-cytoplasm ratio and liver progenitor cell marker expression Activities of CYP1A2, CYP2B6, and CYP3A4 FRG mice 13% [16]
ProliHHs Hepatocytes Wnt3a, N2, B27, N-acetylcysteine, gastrin, EGF, FGF10, HGF, nicotinamide, A83-01, FSK, and Y27632 Progenitor-associated gene expression and biphenotypic cells CYP2B6 activity FRG mice 64 ± 21.8% (at P4) at 4 months 5.8 ± 4.5 mg/ml (at P4) at 4 months [17]
Hep-Orgs Fetal and cryopreserved primary hepatocytes RSPO1 conditioned medium, B27, EGF, N-acetylcysteine, gastrin, CHIR99021, HGF, FGF7, FGF10, A83-01, nicotinamide, Rho inhibitor g-27,632, and TGFα Networks of bile canaliculi, PAS staining, and LDL uptake CYP3A4 activity and CYP2E1 expression FNRG mice 200 μg/ml after 90 days [18]