Generation of hepatic progenitor cells from human hepatocytes using small molecules

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K16643
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Chemical biology
• Research Institution: National Cancer Center Japan
• Principal Investigator: KATSUDA Takeshi 国立研究開発法人国立がん研究センター, 研究所, 研究員 (40732326)
• Co-Investigator(Renkei-kenkyūsha): OCHIYA Takahiro 国立がん研究センター研究所, 分子細胞治療研究分野, 主任分野長 (60192530) ; MATSUZAKI Juntaro 国立がん研究センター研究所, 分子細胞治療研究分野, 特任研究員 (60464864) ; SAITO Yoshimasa 慶応大学, 薬学部・薬学研究科, 准教授 (90360114) ; TAKEUCHI Atsuko 神戸薬科大学, 薬学部, 准教授 (80154970)
• Research Collaborator: 山田 泰弘 日本薬科大学, 教授 ; 山口 智子 慶応大学, 大学院生 ; 保坂 和徳 新潟大学, 大学院生
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: 肝細胞移植 / 肝前駆細胞 / リプログラミング / 低分子化合物 / 肝細胞 / シトクロームP450

Outline of Final Research Achievements

Using small molecule inhibitors, we recently reported that rodent mature hepatocytes can be reprogrammed into progenitor-like phenotype with repopulative capacity. In this study, using the same strategy, we demonstrated that hepatic progenitor cells can be induced from human infant hepatocytes. These cells, named human chemically induced progenitors (hCLiPs), exhibited significant repopulative capacity in injured mouse livers following transplantation, and contributed to reconstruction of the normal liver architecture. We also found that hCLiPs can be redifferentiated into mature hepatocytes in vitro with hepatic inducible factors. These redifferentiated cells can be induced to exhibit cytochrome P450 (CYP) enzymatic activities in response to the CYP inducing molecules with the efficiency comparable with that of primary hepatocytes. Thus, this study contributes to progress in the field of liver cell transplantation therapy and pharmacological research field.

Free Research Field

再生医療、細胞生物学