Long-term survival and functional maintenance of hepatocytes by using a microfabricated cell array

被引:14
作者
Ikeda, Yutaka [1 ]
Jomura, Tomoko [4 ]
Horiuchi, Umeko [1 ]
Saeki, Junko [1 ]
Yoshimoto, Keitaro [1 ]
Ikeya, Takeshi [4 ]
Nagasaki, Yukio [1 ,2 ,3 ]
机构
[1] Univ Tsukuba, Grad Sch Pure & Appl Sci, Dept Mat Sci, Tsukuba, Ibaraki 3058573, Japan
[2] Univ Tsukuba, Grad Sch Comprehens Human Sci, Masters Sch Med Sci, Tsukuba, Ibaraki 3058573, Japan
[3] Univ Tsukuba, Natl Inst Mat Sci, Int Ctr Mat Nanoarchitecton WPI MANA, Satellite Lab, Tsukuba, Ibaraki 3058573, Japan
[4] Transparent Inc, Chiba 2701609, Japan
关键词
Microfabricated cell array; Spheroid; Liver diseases; Cytochrome P450; Albumin secretion;
D O I
10.1016/j.colsurfb.2012.04.022
中图分类号
Q6 [生物物理学];
学科分类号
071011 ;
摘要
We developed a microfabricated cell array of hepatocyte spheroids that showed long-term viability and retained the properties of the parent hepatocytes. Fresh hepatocytes harvested from 8-week-old Wistar rats were cocultured with feeder cells to rapidly form hepatocyte spheroids; these cells retained the spheroidal formation for 42 days. We also evaluated the cellular functions of the hepatocytes such as albumin secretion and metabolic activity of cytochrome P450 (CYP). In spheroids in which hepatocytes were cocultured with feeder cells, these cellular functions were retained even after 42 days. Therefore, this novel coculture will be very useful not only for research on the mechanism and treatment of liver diseases but also for early prediction of hepatocyte toxicity in the pre-clinical phase of drug development. (C) 2012 Elsevier B.V. All rights reserved.
引用
收藏
页码:97 / 100
页数:4
相关论文
共 6 条
[1]   Spheroid array of fetal mouse liver cells constructed on a PEG-gel micropatterned surface: upregulation of hepatic functions by co-culture with nonparenchymal liver cells [J].
Kojima, Ryota ;
Yoshimoto, Keitaro ;
Takahashi, Emiko ;
Ichino, Masahiro ;
Miyoshi, Hirotoshi ;
Nagasaki, Yukio .
LAB ON A CHIP, 2009, 9 (14) :1991-1993
[2]   Two-dimensional multiarray formation of hepatocyte spheroids on a microfabricated PEG-brush surface [J].
Otsuka, H ;
Hirano, A ;
Nagasaki, Y ;
Okano, T ;
Horiike, Y ;
Kataoka, K .
CHEMBIOCHEM, 2004, 5 (06) :850-855
[3]   Nonalcoholic Fatty Liver Disease and Hepatocellular Carcinoma: A Weighty Connection [J].
Starley, Brad Q. ;
Calcagno, Christopher J. ;
Harrison, Stephen A. .
HEPATOLOGY, 2010, 51 (05) :1820-1832
[4]  
U.S. Food and Drug Administration Guidance for Industry, 2006, GUID INT DRUG INT ST
[5]  
WAXMAN DJ, 1998, ARCH BIOCHEM BIOPHYS, V263, P424
[6]   Inverted pattern formation of cell microarrays on poly(ethylene glycol) (PEG) gel patterned surface and construction of hepatocyte spheroids on unmodified PEG gel microdomains [J].
Yoshimoto, Keitaro ;
Ichino, Masahiro ;
Nagasaki, Yukio .
LAB ON A CHIP, 2009, 9 (09) :1286-1289