Challenges of Using iPSCs and New Directions for Improvement

In order to improve iPSC HLCs, focus should be given to the improvement of the phenotype of these cells with comparison to primary human hepatocytes (Fig. 21.2). This may be broken down into pharmacological relevance, that is. 

In addition, incorporation of NPCs into these models including immune cells that are known to play a role in idiosyncratic ADRs will help to produce more physiologically relevant models of hepatotoxicity, as it is important to appreciate that not all hepatotoxicity arises from toxicity to hepatocytes. 

Qassic stress responses, MAPKs, Nrf-2, and organelle-specific responses 

APPLICATION OF PLURIPOTENT STEM CELLS IN DRUG-INDUCED LIVER INJURY SAFETY ASSESSMENT 

Thus far, differentiation of iPSCs to a mature HLC phenotype that is comparable to primary hepatocytes has proven to be challenging. HLCs generated in different studies appeared to be more fetal-like. Small molecules identified by high-throughput screening demonstrated their potential for HLC maturation (increased albumin secretion, CYP activity, and gene expression of ABC transporters), although the mechanisms are unclear (Bohme et al., 1994). 

---