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

被引：228

作者：

Takayama, Kazuo ^{[1
,2
]}

Kawabata, Kenji ^{[2
,3
]}

Nagamoto, Yasuhito ^{[1
,2
]}

Kishimoto, Keisuke ^{[1
,2
]}

Tashiro, Katsuhisa ^{[2
]}

Sakurai, Fuminori ^{[1
]}

Tachibana, Masashi ^{[1
]}

Kanda, Katsuhiro ^{[4
]}

Hayakawa, Takao ^{[5
]}

Furue, Miho Kusuda ^{[6
,7
]}

Mizuguchi, Hiroyuki ^{[1
,2
,8
]}

机构：

[1] Osaka Univ, Grad Sch Pharmaceut Sci, Lab Biochem & Mol Biol, Suita, Osaka 5650871, Japan

[2] Natl Inst Biomed Innovat, Lab Stem Cell Regulat, Osaka 5670085, Japan

[3] Osaka Univ, Grad Sch Pharmaceut Sci, Lab Biomed Innovat, Suita, Osaka 5650871, Japan

[4] Hitachi High Technol Corp, Corp Strategy Div, Corp Projects Ctr, Pharma Business Project, Ibaraki 3128504, Japan

[5] Kinki Univ, Pharmaceut Res & Technol Inst, Osaka 5778502, Japan

[6] Natl Inst Biomed Innovat, Dept Dis Bioresources Res, Lab Embryon Stem Cell Cultures, Osaka 5670085, Japan

[7] Kyoto Univ, Inst Frontier Med Sci, Field Stem Cell Res, Dept Embryon Stem Cell Res, Kyoto 6068507, Japan

[8] Osaka Univ, Ctr Adv Med Engn & Informat, Suita, Osaka 5650871, Japan

来源：

BIOMATERIALS | 2013年 / 34卷 / 07期

基金：

日本学术振兴会;

关键词：

Hepatocyte-like cell; Human ES cell; Human iPS cell; Nanopillar plate; Drug screening; PLURIPOTENT STEM-CELLS; ADENOVIRUS VECTOR; DIFFERENTIATION; LINES; TRANSDUCTION; MECHANISMS; GENERATION; COCULTURE; PROMOTES; SHEETS;

D O I：

10.1016/j.biomaterials.2012.11.029

中图分类号：

R318 [生物医学工程];

学科分类号：

0831 ;

摘要：

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. (C) 2012 Elsevier Ltd. All rights reserved.

引用

页码：1781 / 1789

页数：9

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