Human induced pluripotent stem cells derived hepatocytes: rising promise for disease modeling, drug development and cell therapy

Abstract

Recent advances in the study of human hepatocytes derived from induced pluripotent stem cells (iPSC) represent new promises for liver disease study and drug discovery. Human hepatocytes or hepatocyte-like cells differentiated from iPSC recapitulate many functional properties of primary human hepatocytes and have been demonstrated as a powerful and efficient tool to model human liver metabolic diseases and facilitate drug development process. In this review, we summarize the recent progress in this field and discuss the future perspective of the application of human iPSC derived hepatocytes.

Establishment of hepatic and neural differentiation platforms of Wilson’s disease specific induced pluripotent stem cells

“…Similarly to many other reports of iPSC-based disease modeling, efficient differentiation of patient-specific iPSC into disease-affected cell types represents a critical challenge to the success of the study. Among many established differentiation protocols, efficient differentiation of human pluripotent stem cells into functional hepatocytes is technically challenging, in spite of its tremendous application potential (Yi et al, 2012). In line with many other reports, we observed that the HLC differentiated from patient iPSC resemble many important features to PHH and exhibit functionality in vitro, however, they do not fully match the maturation level of PHH.…”

Human hepatocytes derived from pluripotent stem cells: a promising cell model for drug hepatotoxicity screening

“…One of the main advantages of using iPSCs is that they allow the really impact of genetics on cell responses to drugs to be studied. Generation of iPSCs from clinically identified donors that exhibit different drug sensitivities and metabolizing enzymes would increase the predictivity of toxicity assays (Anson et al 2011;Kia et al 2013;Medine et al 2013;Yi et al 2012) (Fig. 2).…”

“…Perhaps in the future, hepatocytes from iPSCs generated from specific patients afflicted with idiosyncratic hepatotoxicity may provide insights into the role of genetic diversity in DILI (Takayama et al 2014;Mann 2015). Generating panels of human iPSC-derived hepatocytes from individuals with different CYP polymorphisms would also be extremely valuable for drug metabolism, drug-drug interactions and more accurate toxicity predictions in humans of new drugs in preclinical stages to enable more successful clinical trials, which would shorten the timeline and reduce costs (Anson et al 2011;Yi et al 2012;Medine et al 2013;Holmgren et al 2014;Takayama et al 2014;Davidson et al 2015). iPSCs also offer the opportunity to generate liver cells in different maturation stages, as well as the potential to give rise to all the composite cells of the adult liver (Baxter et al 2010;Medine et al 2013).…”

“…The fact that these cells can be derived in a robust reproducible fashion from a wellcharacterized source makes them a most appealing toxicity assessment model. Human PSCs-derived hepatocytes can provide a limitless supply of HLCs for high-throughput screening with minor batch variability from multiple individuals, which helps improve reproducibility and enables individual-specific toxicity to be tested (Katsuda et al 2012;Yi et al 2012;Soldatow et al 2013;Takayama et al 2014).…”

From Human-Induced Pluripotent Stem Cells to Liver Disease Modeling: A Focus on Dyslipidemia

“…Therefore, it was urgent to develop a high-fidelity human hepatocytes model such as hiPSCs. These cells offer promising opportunities for highthroughput drug screening in a cost-effective manner, with enhanced reproducibility and decreased risks of failure during preclinical stages [41]. It is important to note that hiPSCs-derived hepatocytes enable the establishment of a wide spectrum of readily available hepatocyte lines, which represent the potential genetic and epigenetic variations of a human population.…”