Table 2.

Currently investigated, but not yet established, test systems for the human liver metabolism and clearance estimation.

Model system	(most important) feature	Reference
“Simple” 2D or 3D cell cultures
Primary cell co-cultures	Cell-cell interactions	(Guguen-Guillouzo and Guillouzo, 2010)
Embryonic stem cells	Functionality in doubt; Donor variability	(Pal et al., 2012)
Induced pluripotent stem cells	Functionality in doubt; donor variability	(Si-Tayeb et al., 2010)
Spheroid scaffold-free cultures	improved stability and functionality, simple setup	(Gunness et al., 2013) (Vorrink et al 2017)
Scaffold structures without or with flow arrangements
Micropatterned plated cell cultures (e.g. Hepatopac)	improved stability and functionality	(Chan et al., 2013)
HμREL® Biochip (microfluidic flow)	improved stability and functionality, complex setup	(Chao et al., 2009)
Hollow-fiber bioreactor	improved stability and functionality, complex setup	(Zeilinger et al., 2011)
Perfused multi-well bioreactor	improved stability and functionality, complex setup	(Domansky et al., 2010)
Perfused matrix-embedded hepatocyte bioreactor	artificial liver -mimic	(Schmelzer et al., 2010)