Table 1.

Summary of MOCs with applications in disease modelling and ADMET. GLP-1, glucagon-like peptide-1; GLUT, glucose transporter; hiPSC, human induced pluripotent stem cell; qPCR, quantitative polymerase chain reaction.

application	ref.	organ models involved	cell types	drugs studied	endpoints and assays performed
disease modelling (NAFLD)	[80]	gut, liver	Caco-2, HepG2	—	• microscopic high-content analysis • mRNA sequencing • gene expression
disease modelling (hepatic steatosis)	[81]	gut, liver	Caco-2, HepG2	turofexorate isopropyl (XL-335), metformin	• cell viability • permeability assay, • gut–liver chip-based drug screening
disease modelling (diabetes)	[65]	pancreas	human cadaveric islet and SC-β cell	—	hydrodynamic islet trapping insulin quantification
	[91]	pancreas–liver	primary rat islets and hepatocytes	—	RTqPCR assays
	[90]	intestine–pancreas	rat β-cell line INS-1, GLUTag cell line	GLP-1 analogues and natural insulin and GLP-1	ELISA immunoflourescence staining
ADMET	[73]	liver, brain	human liver spheroids and neurospheres	2,5-hexanedione	qRT-PCR toxicity assay endpoint tissue culture analysis
	[94]	liver, skin	HepaRG cell line, skin biopsies	troglitazone	multi-tissue sensitivity assay LDH assay
	[95]	human intestine, liver, skin, kidney	primary human intestinal constructs, HepaRG, skin biopsy construct, human proximal tubule cell line	selected drug candidates.	RNA quantification systemic tissue viability and barrier organ integrity
	[96]	brain, pancreas, liver, lung, heart, gut, endometrium	tissue constructs	tolcapone	metabolite profiling metabolomics
	[97]	liver, heart	iPS-derived cardiomyocytes, primary hepatocytes	cyclophosphamide, terfenadine	biomarker and enzyme expression electrical activity measurements drug quantification via HPLC-MS
	[98]	liver, heart	hiPSCs	cisapride, norcisapride, ketoconazole	drug transport studies, qPCR drug metabolism assays
	[99]	liver, heart, lung, endothelium, brain, testes	primary human cells, hiPSCs, cell line	capecitabine	drug toxicity assays
	[100]	liver, breast, lung, intestine	primary cells and cell lines	capecitabine	PK-PD studies, toxicity, and metabolism studies
	[101]	liver, kidney	cell line	ciclosporin, rifampicin	biomarker analysis protein expression
	[107]	testes, liver	primary human testicular organoids, HepaRG cells	cyclophosphamide	immunofluorescence hormone measurements
	[109]	liver, skin	human epidermal cells, HepaRG	hyperforin, permethrin	gene expression qPCR mass spectrometry
	[111]	intestine, liver, kidney; bone marrow, liver, kidney	Caco-2, primary human hepatocytes, human renal proximal tubule cells, primary bone marrow progenitor cells	nicotine, cisplatin	barrier function assessment mass sprectrometry flow cytometry