一种新型的小体积双腔微加工平台,用于评估药物代谢和毒性。

S. S. Bale, G. Sridharan, I. Golberg, L. Prodanov, W. McCarty, O. B. Usta, Rohit Jindal, M. Yarmush
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引用次数: 13

摘要

为了评估药物和代谢物对靶器官的疗效,必须包括肝细胞的代谢功能,并评估代谢物对肝细胞和目标器官的影响。在此,我们开发了一种由膜分隔的双室微制造装置,使肝细胞和癌细胞之间能够通信。创建的微尺度环境使细胞在低培养基与细胞比例下共同培养,从而导致更高的代谢物形成和快速积累,这在传统的平板培养或其他相互关联的模型中由于培养量较大而丢失。我们通过肝细胞对替加氟的代谢导致癌细胞毒性来证明该系统的功效。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
A novel low-volume two-chamber microfabricated platform for evaluating drug metabolism and toxicity.
To evaluate drug and metabolite efficacy on a target organ, it is essential to include metabolic function of hepatocytes, and to evaluate metabolite influence on both hepatocytes and the target of interest. Herein, we have developed a two-chamber microfabricated device separated by a membrane enabling communication between hepatocytes and cancer cells. The microscale environment created enables cell co-culture in a low media-to-cell ratio leading to higher metabolite formation and rapid accumulation, which is lost in traditional plate cultures or other interconnected models due to higher culture volumes. We demonstrate the efficacy of this system by metabolism of tegafur by hepatocytes resulting in cancer cell toxicity.
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