Table 6.

Examples of multicellular static and microfluidic liver models for absorption, distribution, metabolism, excretion, and toxicity (ADMET) testing

Model	Application	Advantage	Disadvantage	References
Static models
Co-culture spheroids	Stellate cell activation	Long term 3D culturing with improved drug metabolism and output of albumin, urea	Specialized plates to from spheroids, specialized culturing techniques	67
Co-culture micropatterned primary hepatocytes with fibroblasts	Hepatotoxicity Metabolite ID Disease models	Hepatocytes maintain differentiated function 2–3 wk	2D cultures, specialized plates	65,68
Four-cell spheroids primary hepatocytes, primary liver NPC	Hepatotoxicity Metabolite ID	Hepatocytes maintain differentiated function >3 wk, 3D, immune-mediated toxicity	Specialized culturing techniques	69
3D microfluidic, multicellular liver models
Primary hepatocytes, endothelial cells	Hepatotoxicity	Hepatocytes maintain differentiated function >3 wk, microfluidic improves function	Specialized culturing techniques, perfusion system	70
Hepatocytes, endothelial cells, stellate cells, Kupffer-like immune cells	PK, toxicity, therapeutic intervention, liver disease model	Hepatocytes maintain differentiated function >3 wk, immune-mediated toxicity, fibrosis activation microfluidic improves function	Specialized culturing techniques, perfusion system	48,51,71

Abbreviations: 2D, 2 dimensional; 3D, 3 dimensional; NPC, non parenchymal cells; PK, pharmacokinetic.