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.

人肝细胞是药代动力学和药物安全性评估的基本细胞类型。然而，广泛使用的具有肝功能个体差异的原代肝细胞在培养中迅速丧失了这些功能。肝细胞系使用方便，但肝功能低下。人类诱导的多能干细胞（hiPS）可以扩增并可能分化为任何细胞或组织，包括肝脏。HiPS细胞来源的肝细胞样细胞（hiPSHeps）有望广泛用作稳定的功能性人类肝细胞。许多实验室正在研究使用hiPS细胞分化肝细胞的方法，但衍生细胞仍具有未成熟的肝功能。在本文中，我们描述了常规肝细胞的当前用途和局限性，