3D spheroid culture of hESC/hiPSC-derived hepatocyte-like cells for drug toxicity testing

作者：Takayama Kazuo; Kawabata Kenji; Nagamoto Yasuhito; Kishimoto Keisuke; Tashiro Katsuhisa; Sakurai Fuminori; Tachibana Masashi; Kanda Katsuhiro; Hayakawa Takao; Furue Miho Kusuda; Mizuguchi Hiroyuki^*

来源：Biomaterials, 2013, 34(7): 1781-1789.

DOI：10.1016/j.biomaterials.2012.11.029

• Hepatocyte-like cell
• Human ES cell
• Human iPS cell
• Nanopillar plate
• Drug screening

Although it is expected that hepatocyte-like cells differentiated from human embryonic stem (ES) cells or induced pluripotent stem (iPS) cells will be utilized in drug toxicity testing, the actual applicability of hepatocyte-like cells in this context has not been well examined so far. To generate mature hepatocyte-like cells that would be applicable for drug toxicity testing, we established a hepatocyte differentiation method that employs not only stage-specific transient overexpression of hepatocyte-related transcription factors but also a three-dimensional spheroid culture system using a Nanopillar Plate. We succeeded in establishing protocol that could generate more matured hepatocyte-like cells than our previous protocol. In addition, our hepatocyte-like cells could sensitively predict drug-induced hepatotoxicity, including reactive metabolite-mediated toxicity. In conclusion, our hepatocyte-like cells differentiated from human ES cells or iPS cells have potential to be applied in drug toxicity testing.

• 出版日期2013-2