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一种用于评估药物代谢和毒性的新型小体积双腔微制造平台。

A novel low-volume two-chamber microfabricated platform for evaluating drug metabolism and toxicity.

作者信息

Bale Shyam Sundhar, Sridharan Gautham Vivek, Golberg Inna, Prodanov Ljupcho, McCarty William J, Usta Osman Berk, Jindal Rohit, Yarmush Martin L

机构信息

Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School and Shriners Hospital for Children, Boston, MA 02114, USA.

Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School and Shriners Hospital for Children, Boston, MA 02114, USA; Department of Biomedical Engineering, Rutgers University, Piscataway, NJ 08854, USA.

出版信息

Technology (Singap World Sci). 2015 Dec;3(4):155-162. doi: 10.1142/S2339547815200034. Epub 2015 Apr 21.

Abstract

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.

摘要

为了评估药物及其代谢产物对靶器官的功效,纳入肝细胞的代谢功能以及评估代谢产物对肝细胞和感兴趣靶标的影响至关重要。在此,我们开发了一种双室微制造装置,该装置由一层膜隔开,使肝细胞和癌细胞之间能够进行通讯。所创建的微观环境能够以低培养基与细胞比例进行细胞共培养,从而导致更高的代谢产物形成和快速积累,而在传统平板培养或其他相互连接的模型中,由于培养体积较大,这种情况会消失。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。

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