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基于微流控技术的用于药物发现的器官/芯片上的人体模型

Organ/body-on-a-chip based on microfluidic technology for drug discovery.

作者信息

Kimura Hiroshi, Sakai Yasuyuki, Fujii Teruo

机构信息

Department of Mechanical Engineering, School of Engineering, Tokai University, 4-1-1, Kitakaname, Hiratsuka, 259-1292, Kanagawa, Japan; Micro/Nano Technology Center, Tokai University, 4-1-1, Kitakaname, Hiratsuka, 259-1292, Kanagawa, Japan.

Department of Chemical System Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo, 113-8654, Japan; International Research Center on Integrative Biomedical Systems (CIBiS), Institute of Industrial Science, The University of Tokyo, 4-6-1, Komaba, Meguro, Tokyo, 153-8505, Japan.

出版信息

Drug Metab Pharmacokinet. 2018 Feb;33(1):43-48. doi: 10.1016/j.dmpk.2017.11.003. Epub 2017 Nov 13.

Abstract

Although animal experiments are indispensable for preclinical screening in the drug discovery process, various issues such as ethical considerations and species differences remain. To solve these issues, cell-based assays using human-derived cells have been actively pursued. However, it remains difficult to accurately predict drug efficacy, toxicity, and organs interactions, because cultivated cells often do not retain their original organ functions and morphologies in conventional in vitro cell culture systems. In the μTAS research field, which is a part of biochemical engineering, the technologies of organ-on-a-chip, based on microfluidic devices built using microfabrication, have been widely studied recently as a novel in vitro organ model. Since it is possible to physically and chemically mimic the in vitro environment by using microfluidic device technology, maintenance of cellular function and morphology, and replication of organ interactions can be realized using organ-on-a-chip devices. So far, functions of various organs and tissues, such as the lung, liver, kidney, and gut have been reproduced as in vitro models. Furthermore, a body-on-a-chip, integrating multi organ functions on a microfluidic device, has also been proposed for prediction of organ interactions. We herein provide a background of microfluidic systems, organ-on-a-chip, Body-on-a-chip technologies, and their challenges in the future.

摘要

尽管动物实验在药物发现过程的临床前筛选中不可或缺,但仍存在诸如伦理考量和物种差异等各种问题。为了解决这些问题,人们积极探索使用人源细胞的基于细胞的检测方法。然而,由于在传统的体外细胞培养系统中,培养的细胞往往无法保留其原始的器官功能和形态,因此准确预测药物疗效、毒性和器官相互作用仍然很困难。在作为生物化学工程一部分的微全分析系统(μTAS)研究领域,基于微加工构建的微流控装置的芯片器官技术,作为一种新型的体外器官模型,近年来得到了广泛研究。由于使用微流控装置技术可以在物理和化学上模拟体外环境,因此使用芯片器官装置可以实现细胞功能和形态的维持以及器官相互作用的复制。到目前为止,肺、肝、肾和肠道等各种器官和组织的功能已经作为体外模型得以再现。此外,还提出了一种在微流控装置上整合多器官功能的芯片人体,用于预测器官相互作用。我们在此提供微流控系统、芯片器官、芯片人体技术的背景及其未来面临的挑战。

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