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
| Â | 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 | |
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] |