幹細胞を用いた新規肝細胞モデルの構築とその創薬応用

抄録

Most drugs are metabolized and detoxified in the liver. Therefore, human hepatocytes are essential for pharmacokinetic and toxicity tests in pharmaceutical research. Although primary human hepatocytes (PHHs) are the main cell source used as a human liver model, major drawbacks include the limited supply of PHHs and their functional deterioration due to long-term culture. Many studies have been conducted to overcome these problems or develop new hepatocyte sources. In particular, stem cells with cell proliferative potential are expected to be useful in pharmaceutical research, as they can supply many homogeneous specific somatic cells through differentiation and maturation. Here, we describe recent advances in the use of hepatocyte-like cells derived from human embryonic stem (ES) cells or induced pluripotent stem (iPS) cells and human liver organoids. The hepatocyte differentiation method from human ES/iPS cells by some strategies has been improved. However, the hepatic functions in human hepatocyte-like cells derived from ES/iPS cells are still lower than those in PHHs. Similarly, although human liver organoids show long-term proliferation, their hepatic functions remain low. Human ES/iPS cells and liver organoids could overcome the limited supply of PHHs, but improving their hepatic function is essential. We believe that stem cell culture technology will be useful for generating a functional hepatocyte source for medical applications.