Open Access
Organs-on-a-Chip Volume 3, November 2021, 100010

In vitro nonalcoholic fatty liver disease model with cyclo-olefin-polymer-based microphysiological systems  

Xiaopeng Wen1, Koki Yoshimoto1,2,3, Makoto Yamanaka4, Shiho Terada1, Ken-ichiro Kamei1,5,6

1Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Yoshida-Ushinomiya-cho, Sakyo-ku, Kyoto, 606-8501, Japan
2Department of Biosystems Science, Institute for Frontier Life and Medical Sciences, Kyoto University, Shogoin-Kawara-cho, Sakyo-ku, Kyoto, 606-8397, Japan
3Laboratory of Cellular and Molecular Biomechanics, Graduate School of Biostudies, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto, 606-8397, Japan
4Incubation Center Organs on Chip Project, Ushio INC, 1-6-5 Marunouchi, Chiyoda-ku, Tokyo, 100-8150, Japan
5Wuya College of Innovation, Shenyang Pharmaceutical University, Liaoning, 110016, People's Republic of China
6Department of Pharmaceutics, Shenyang Pharmaceutical University, Liaoning, 110016, People's Republic of China   


近年、細胞を用いたin vitro試験において、より詳細な評価ができるマイクロ生体模倣システム(MPS)と呼ばれるマイクロ流体チップを用いた検討が注目されている。一方で、従来MPSの開発においてはポリジメチルシロキサン(PDMS)というシリコーンゴム系の材料がよく用いられている。しかし、PDMSは疎水性分子を吸収してしまうことから、例えば遊離脂肪酸(FFA)を原因物質とする非アルコール性脂肪性肝疾患(NAFLD)モデルへの適応において問題となっていた。そこで本研究では、FFAの吸収がない材料としてシクロオレフィンポリマー(COP)から構成されたチップを採用し、in vitro NAFLDモデルを製作、評価を実施した。非アルコール性脂肪性肝疾患(NAFLD)は最も一般的な慢性肝疾患の1つである。実用的なMPSにより新しい診断や治療薬の開発に貢献できると期待している。 


In recent years, there has been a growing interest in using microfluidic chips called micro-physiological systems (MPS), which enable more detailed evaluation in in-vitro studies using cells. On the other hand, polydimethylsiloxane (PDMS), a silicone rubber-based material, is often used in developing MPS. However, PDMS absorbs hydrophobic molecules, which is a problem in applying several applications, such as non-alcoholic fatty liver disease (NAFLD) models in which free fatty acids (FFAs) are the causative agent. In this study, we employed chips made of cyclo-olefin polymer (COP) as a material that does not absorb FFAs, and developed and evaluated in vitro NAFLD model. Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases. Practical MPS will contribute to the development of new diagnostic and therapeutic agents. 



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