Sano Emi, Deguchi Sayaka, Matsuoka Naoki, Tsuda Masahiro, Wang Mengyang, Kosugi Kaori, Mori Chihiro, Yagi Keisuke, Wada Aya, Yamasaki Shinsuke, Kawai Tsuyoshi, Yodogawa Masahide, Mizuguchi Hiroyuki, Nakazawa Norihito, Yamashita Fumiyoshi, Torisawa Yu-Suke, Takayama Kazuo
Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto 606-8507, Japan.
Department of Micro Engineering, Kyoto University, Kyoto 615-8540, Japan.
ACS Omega. 2021 Sep 15;6(38):24859-24865. doi: 10.1021/acsomega.1c03719. eCollection 2021 Sep 28.
Polydimethylsiloxane (PDMS) is widely used to fabricate microfluidic organs-on-chips. Using these devices (PDMS-based devices), the mechanical microenvironment of living tissues, such as pulmonary respiration and intestinal peristalsis, can be reproduced . However, the use of PDMS-based devices in drug discovery research is limited because of their extensive absorption of drugs. In this study, we investigated the feasibility of the tetrafluoroethylene-propylene (FEPM) elastomer to fabricate a hepatocyte-on-a-chip (FEPM-based hepatocyte chip) with lower drug absorption. The FEPM-based hepatocyte chip expressed drug-metabolizing enzymes, drug-conjugating enzymes, and drug transporters. Also, it could produce human albumin. Although the metabolites of midazolam and bufuralol were hardly detected in the PDMS-based hepatocyte chip, they were detected abundantly in the FEPM-based hepatocyte chip. Finally, coumarin-induced hepatocyte cytotoxicity was less severe in the PDMS-based hepatocyte chip than in the FEPM-based hepatocyte chip, reflecting the different drug absorptions of the two chips. In conclusion, the FEPM-based hepatocyte chip could be a useful tool in drug discovery research, including drug metabolism and toxicity studies.
聚二甲基硅氧烷（PDMS）被广泛用于制造微流控芯片器官。使用这些装置（基于PDMS的装置），可以重现活组织的机械微环境，如肺呼吸和肠道蠕动。然而，基于PDMS的装置在药物发现研究中的应用受到限制，因为它们对药物有广泛的吸收。在本研究中，我们研究了四氟乙烯-丙烯（FEPM）弹性体制备具有较低药物吸收的芯片上肝细胞（基于FEPM的肝细胞芯片）的可行性。基于FEPM的肝细胞芯片表达药物代谢酶、药物结合酶和药物转运蛋白。此外，它还可以产生人白蛋白。虽然在基于PDMS的肝细胞芯片中几乎检测不到咪达唑仑和布呋洛尔的代谢物，但在基于FEPM的肝细胞芯片中却大量检测到。最后，香豆素诱导的肝细胞毒性在基于PDMS的肝细胞芯片中比在基于FEPM的肝细胞芯片中轻，这反映了两种芯片不同的药物吸收情况。总之，基于FEPM的肝细胞芯片可能是药物发现研究中的一个有用工具，包括药物代谢和毒性研究。
