Table 4.
Application and evaluation indicators
| Cell type | Culture mediuma | Structure | Applications | Biomarkers | References |
|---|---|---|---|---|---|
| HepaRG | High Glucose Dulbecco’s Modified Eagle Medium (DMEM) with dimethyl sulfoxide (DMSO) medium | Scaffold | Transplantation | Albumin, α-1 antitrypsin, factor VII, factor IX, CYP1A2, CYP3A4, alanine aminotransferase (ALT), aspartate aminotransferase (AST), direct bilirubin (DBIL), gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), albumin/globulin ration (A/G) | [73] |
| HepG2, HUVEC | FBS and penicillin-streptomycin solution mixed in fresh DMEM | Hepatic lobule spheroids | Transplantation | MRP2, albumin, β-catenin, P-β-catenin, α-1 antitrypsin, urea, CYP3A4, CYP1A2, CYP2B6, CD31 | [102] |
| Mesenchymal stem cells (MSCs) | Heparinized acellular extracellular matrix and mesenchymal stem cell culture medium | Spheroids | Transplantation | albumin (ALB), aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TIBL), FOXA2, NR1I2, SLC27A5, INS2, CYP1A1, CYP3A9, GPX3, AKR1D1 | [75] |
| HepaRG, stellate cells (LX-2), HUVEC | William’s E medium with fetal bovine serum Hyclone III, penicillin, streptomycin, human insulin, l-glutamine, hydrocortisone hemisuccinate and DMSO | Scaffold | Liver fibrosis induction | Albumin, ACTA2, COL1A1, MMP2, TIMP1, Cytochrome P450 isoforms (CYP3A4, CYP2B6, CYP2E1, CYP2C9, CYP2C19) | [82] |
| Primary human hepatocytes, HSCs, HUVEC, Kuffer cells | DMSO was spiked into the TGF-β1 dosing solution and standard culture medium | Scaffold | Liver fibrosis induction | miR-122, albumin, urea, lactate dehydrogenase (LDH) | [207] |
| HepG2 | DMEM with fetal bovine serum | Hepatic lobule organoids | Hepatocellular carcinoma | Albumin, E-cadherin, matrix metalloproteinases (MMP2 MMP9), AFP, Twist-related protein 1 (TWIST1) | [208] |
| Primary hepatocellular carcinoma | DMEM/F12, penicillin/streptomycin, GlutaMAX, HEPES, B27, N2, N-acetyl-l-cysteine, nicotinamide, recombinant human (Leu15)-gastrin I, recombinant human EGF, recombinant human FGF10, recombinant human HGF, forskolin, A8301, Y27632, dexamethasone | Scaffold | Hepatocellular carcinoma | Ki-67, AFP, Raf-1, VEGFR1, VEGFR2 | [209] |
| HepaRG | William’s E medium with fetal bovine serum, l-Glutamine, recombinant human insulin, hydrocortisone hemisuccinate, penicillin/streptomycin, DMSO | Scaffold | Viral transcription | Albumin, CYP3A4, lactate dehydrogenase (LDH), adenoviral DNA | [210] |
| HepG2 | Minimum essential medium (MEM) α supplemented with FBS and antibiotic–antimycotic | Spheroid | Drug-induced hepatotoxicity | MPT, cytosolic calcium, caspase-3 | [28] |
| Hepatocytes, endothelial cells, Kupffer cells, and stellate cells | William’s E medium containing GlutaMAX, ITS+ Premix [human recombinant insulin, human transferrin, selenous acid, BSA, and linoleic acid], dexamethasone, ascorbic acid, fetal bovine serum, and penicillin/streptomycin | Organ-on-a-chip | Drug toxicity, predict drug-induced liver injury (DILI) | Cytochrome P450 isoforms (CYP1A, CYP2B, and CYP3A), MRP2, miR122, α-GST, keratin 18, ALT, AST, GLDH |
[66] |
| Human adipose-derived mesenchymal stem cells (ADMSCs), HUVEC, human hepatic stellate cells (HHSCs) | HiPer high glucose Dulbecco’s Modified Eagle Medium, containing fetal bovine serum, l-glutamine, basic fibroblast growth factor, endothelial cell growth supplement, stellate cell growth supplement | Hepatic lobule organoids | Drug toxicity, drug screening | Cytochrome P450, albumin, cytokeratin 18, CYP2E1, fibronectin, HNF4α markers, α-fetoprotein (AFP) | [170] |
| Human pluripotent stem cell (hPSC) | Advanced DMEM/F12 supplemented with GlutaMAX, HEPES, B27, BSA, N-acetyl-L-cysteine, [Leu15]-gastrin I human, A83–01, DAPT, 3 μM dexamethasone, FGF19, BMP7 and HGF. For suspension culture, media were supplemented with Matrigel | Spheroid | Drug-induced liver injury (DILI) | Cytochrome P450, albumin, urea | [5] |
| HepaRG | William’s E medium supplemented with L-Glutamine, fetal bovine serum, hydrocortisone hemisuccinate, recombinant human insulin, penicillin/streptomycin and DMSO | Scaffold | Drug toxicity | lactate dehydrogenase (LDH), albumin, urea | [211] |
a
The culture medium in Table 4 is all the components of the co-culture medium, among which DMSO is mostly used after 1–2 weeks to induce differentiation.