Immortalized Human Hepatocytes-Myc

Immortalized human hepatocytes (IHHs) constitute a rationally engineered alternative cell source positioned strategically between the gold-standard primary human hepatocytes (PHHs) and hepatoma-derived lines. Their scientific advantage is dual: they overcome the critical supply bottleneck of PHHs-plagued by scarcity, donor variability, and rapid functional dedifferentiation-while avoiding the metabolic inadequacy and tumorigenic background endemic to HepG2/Huh7 models.

Functionally superior to carcinoma lines - Unlike HepG2, IHHs retain inducible cytochrome P450 (CYP3A4, CYP2C, CYP1A2) and authentic acute-phase response (IL-6-stimulated fibrinogen upregulation with reciprocal albumin modulation), demonstrating hepatic polarity with bile canaliculi-like vacuoles and correct localization of efflux transporters (MDR1, MRP2). Select lines (HepZ, HepLL) exhibit albumin secretion and ureagenesis at levels statistically indistinguishable from short-term PHH cultures.

Engineered for biorelevance - IHHs demonstrate exceptional tolerance to pathophysiological insults-HepLi-2 cells sustain CYP3A4/2E1 expression and ammonia/lidocaine clearance after 24 h exposure to acute-on-chronic liver failure plasma, a stress lethal to many hepatoma lines. In 3D radial-flow bioreactors, OUMS-29 cells increase albumin output 6-fold over monolayer and sustain CYP3A4-mediated metabolism beyond 29 days, directly enabling chronic toxicology and drug screening paradigms impossible with PHH.

Thus, IHHs represent not merely a PHH surrogate, but a mechanistically tractable, scalable, and increasingly safe platform for pharmacotoxicology, bioartificial liver engineering, and human-relevant disease modeling where PHH are unobtainable and carcinoma cells unreliable.