3D In Vitro Human Organ Mimicry Devices for Drug Discovery, Development, and Assessment

Table 1

Summary of recent advancements hepatotoxicity testing including the type of drug, the application, the applied cell lines, and the kinetics.

Drug type	Application	Applied cell lines	Kinetics	Ref(s)
Acetaminophen, clozapine, olanzapine, fialuridine, entecavir, aminophenol	Biotransformation, hepatotoxicity	Human hepatocytes from donors	7 days of culture, 48 hr stimuli	[32]
Amiodarone, acetaminophen	Hepatotoxicity due to mitochondrial respiration analysis	HepG2/C3	28 days	[39]
Acetaminophen-omeprazol, acetaminophen-rifampicina, acetaminophen-ciprofloxacin	Drug-drug interaction	HepG2, HUVEC EA.hy926, stellate, U937		[38]
Acetaminophen	Hepatoxicity	HepG2/C3	30 days	[23]
Acetaminophen, isoniazid, rifampicin	Drug-drug interaction, hepatoxicity	Lobule-like HepG2, HAEC	4 days	[136]
Diclofenac	Biotransformation	Multicellular platform: Hu8150 and HK8160	7 days	[30]
Phenacetin, diclofenac, lidocaine, ibuprofen, propranolol, prednisolone	Biotransformation variability	Human primary hepatocytes from donors	7 days	[31]
Bupropion/2-phenyl-2-(1-piperidinyl)propane), tolbutamide/sulphafenazole, omeprazole/benzylnirvanol, testosterone/ketoconazole	Development of CYP450 inhibitors	HepaRG	24 hrs	[26]
Warfarina, dasatinib	Drug-drug interaction	HepaRG	24 hrs	[27]
Midazolam, phenacetin, acetaminophen	Biotransformation	Human primary hepatocytes	13 days	[35]
Tolbutamide, testosterone	Hepatic clearance by CYP3A1 and CYP2C11	Rat hepatocyte primary cell culture	15 days	[137]
Adaptaquin (HIF PHD inhibitors)	Hepatotoxicity	HepaRG	48 hrs	[138]
Adaptaquin and analogs	Biotransformation, hepatotoxicity	HepaRG	24 hrs	[36]
Rifampin, ketoconazole	Hepatotoxicity	Hepatic stellate cells isolated from rat	~14 days	[42]
Vitamin D	Biotransformation	HepG2 cells, RPTEC	~5 days	[139]
Vitamin E (-tocoferol)	Biosynthesis of metabolites to target 5-lipoxygenase	Human-liver-sinusoid, HepaRG cells, HUVEC, human monocyte (PBM)	~5 days	[40]
Ethanol	Detoxification and hepatotoxicity	HepG2	4 days	[24]

CYP450: cytochrome P450; HepG2/C3: human hepatocellular carcinoma/complement factor 3; HUVEC: human umbilical vein cell line; EA.hy926: endothelial cell; U937: human histiocytic lymphoma; HAEC: human aortic endothelial cell line; Hu8150: primary human hepatocytes; HK8160: human Kupffer cells; HepaRG: hepatic biprogenitor cell line; CYP3A1: cytochrome P450 3A1; CYP2C11: cytochrome P450 2C11; RPTEC: renal proximal tubule epithelial cells; PBM: peripheral blood mononuclear cells.