Two-dimensional multiarray formation of hepatocyte spheroids on a microfabricated PEG-brush surface.
A two-dimensional microarray of ten thousand (100 x 100) hepatocyte heterospheroids, underlaid with endothelial cells, was successfully constructed with 100 microm spacing in an active area of 20 x 20 mm on microfabricated glass substrates that were coated with poly(ethylene glycol) brushes. Cocultivation of hepatocytes with endothelial cells was essential to stabilize hepatocyte viability and liver-specific functions, allowing us to obtain hepatocyte spheroids with a diameter of 100 microm, functioning as a miniaturized liver to secret albumin for at least one month. The most important feature of this study is that these substrates are defined to provide an unprecedented control of substrate properties for modulating cell behavior, employing both surface engineering and synthetic polymer chemistry. The spheroid array constructed here is highly useful as a platform of tissue and cell-based biosensors and detects a wide variety of clinically, pharmacologically, and toxicologically active compounds through a cellular physiological response.
Otsuka
Hidenori
H
Department of Materials Science and Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Tokyo 113-8656, Japan.
Hirano
Akihiro
A
Nagasaki
Yukio
Y
Okano
Teruo
T
Horiike
Yasuhiro
Y
Kataoka
Kazunori
K
D000818:Animals; D015374:Biosensing Techniques; D002478:Cells, Cultured; D042783:Endothelial Cells; D022781:Hepatocytes / Q000166:cytology*; D008111:Liver Function Tests; D020411:Oligonucleotide Array Sequence Analysis; D011092:Polyethylene Glycols / Q000737:chemistry*; D051381:Rats; D018874:Spheroids, Cellular / Q000166:cytology*; D013997:Time Factors
D011092:Polyethylene Glycols