Abstract
Improvements in the hepatobiliary differentiation of stem cells have made induced pluripotent stem cell (iPSC) a valuable tool for liver developmental research and drug discovery. Patient-derived iPSC provides an expandable source of hepatocyte-like cells as an alternative to primary hepatocytes. Various iPSC models have been established in recent years to address hereditary and rare diseases of the human hepatobiliary system. These models recapitulate the disease phenotypes that are critical in investigating their pathogenesis and drug interactions. The complexity and variations in human metabolism challenge the "one-size-fits-all solution" in drug design. Traditional hepatotoxicity testing approaches often overlook patient-specific features. Idiosyncratic drug-induced hepatoxicity remains a major cause of liver damage and drug withdrawals. Animal models used in current drug developments remain costly and insufficient in assessing hepatoxicity. Only 8% of the investigational drugs that succeed in animal testing also pass human trials. iPSC-derived hepatocyte-like cells and systems hold a promising future in elucidating hepatobiliary pathogenesis and evaluating potential drugs for both the general population and specific patients.
Original language | English (US) |
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Title of host publication | iPSCs - State of the Science |
Publisher | Elsevier |
Pages | 95-109 |
Number of pages | 15 |
ISBN (Electronic) | 9780323857673 |
ISBN (Print) | 9780323856454 |
DOIs | |
State | Published - Jan 19 2022 |
Keywords
- Cholangiocyte
- Cholangiocyte differentiation
- Cholangiocytes
- Definitive endoderm
- Disease modeling
- Drug discovery
- Hepatocyte differentiation
- Hepatocyte-like cells
- Hepatocytes
- Hepatotoxicity
- Idiosyncratic drug reaction
- IPSC
- Liver development
- Liver disease
- Regenerative medicine
ASJC Scopus subject areas
- General Agricultural and Biological Sciences
- General Biochemistry, Genetics and Molecular Biology