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Human induced pluripotent stem cell-derived hepatocytes and their culturing methods to maintain liver functions for pharmacokinetics and safety evaluation of pharmaceuticals.

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Human hepatocytes are very important 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… Click to show full abstract

Human hepatocytes are very important 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 type of cell or tissue, including the liver. HiPS cell-derived hepatocyte like cells (hiPS-Heps) are expected to be increasingly used as consistently 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, evaluate 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: evaluation pharmaceuticals; liver functions; safety evaluation; pharmacokinetics safety; cell

Journal Title: Current pharmaceutical biotechnology
Year Published: 2020

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