Human-Induced Pluripotent Stem Cell-Derived Hepatocytes and their Culturing Methods to Maintain Liver Functions for Pharmacokinetics and Safety Evaluation of Pharmaceuticals

Author(s): Tomoaki Inoue, Norihiko Iwazaki*, Tetsuro Araki, Hiroko Hitotsumachi

Journal Name: Current Pharmaceutical Biotechnology

Volume 21 , Issue 9 , 2020


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Abstract:

Human hepatocytes are essential cell types for pharmacokinetics and the safety evaluation of pharmaceuticals. However, widely used primary hepatocytes with individual variations in liver function lose those functions rapidly in culture. Hepatic cell lines are convenient to use but have low liver functions. Human-Induced Pluripotent Stem (hiPS) cells can be expanded and potentially differentiated into any cell or tissue, including the liver. HiPS cell-derived Hepatocyte-Like Cells (hiPSHeps) are expected to be extensively used as consistent functional human hepatocytes. Many laboratories are investigating methods of using hiPS cells to differentiate hepatocytes, but the derived cells still have immature liver functions. In this paper, we describe the current uses and limitations of conventional hepatic cells, evaluating the suitability of hiPS-Heps to pharmacokinetics and the safety evaluation of pharmaceuticals, and discuss the potential future use of non-conventional non-monolayer culture methods to derive fully functional hiPS-Heps.

Keywords: hiPS-Heps, primary human hepatocytes (PHHs), drug-induced liver injury (DILI), cytochrome P450, HepG2, microphysiological systems.

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Article Details

VOLUME: 21
ISSUE: 9
Year: 2020
Page: [773 - 779]
Pages: 7
DOI: 10.2174/1389201021666200131123524
Price: $65

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