TABLE II.
Major functions of different liver cell types that can be measured within engineered devices.
| Hepatocyte functions (method) | LSEC functions (method) | KC functions (method) | HSC functions (method) |
|---|---|---|---|
| • Protein synthesis: albumin, transferrin, and alpha-1 antitrypsin (AAT) secretions [enzyme-linked immunosorbant assay (ELISA)] | • Factor VIII secretion (ELISA) | • Tumor necrosis factor alpha and interleukin-6 secretion following 24-h stimulation with lipopolysaccharide (ELISA) | • Lipid/vitamin A droplets (fluorescent stain)—indicates quiescent phenotype |
| • Ammonia detoxification: urea secretion (colorimetric kit) | • Cell surface markers: CD31 and CD32b/SE-1 (immunostaining) | • Phagocytosis (fluorescent bioparticle assay) | • Protein markers Desmin, α-smooth muscle actin (α-SMA) (immunostaining)—high α-SMA is indicative of an activated or myofibroblastic HSC phenotype |
| • Drug metabolism enzyme activities: CYP1A2, 2A6, 2B6, 2D6, 2C8, 2C9, 2C19, 3A4, UGT, and SULT (fluorescent and luminescent metabolites of substrates and detection of substrate metabolites via LC-MS/MS) | • Fenestrae in sinusoidal endothelial cells (scanning electron microscopy) | • Surface markers: CD68 and CD14 (immunostaining) | |
| • Carbohydrate metabolism: de novo glucose secretion (gluconeogenesis) ± hormones (insulin and glucagon) (colorimetric kit) | |||
| • Lipid metabolism: neutral lipid accumulation (fluorescent stain) | |||
| • Transporter functions: OATP1B1/1B3/2B1, OCT1, OAT2/7, NTCP, MRP2/3/4/6, BSEP, P-gp, BCRP, and MATE1 (fluorescent drug and bile analogs, radiolabeled drugs) | |||
| • Toxicity: release of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in supernatants |