How multi-organ microdevices can help foster drug development.
How multi-organ microdevices can help foster drug development.
复制标题
DOI：
10.1016/j.addr.2013.12.003
复制
发表时间：
2014-04
影响因子：
16.1
通讯作者：
Shuler, Michael L.
中科院分区：
文献类型：
--
作者：
Esch, Mandy B.;Smith, Alec S. T.;Prot, Jean-Matthieu;Oleaga, Carlota;Hickman, James J.;Shuler, Michael L.
关键词：
多器官微器件能够模拟体外代谢物从一个组织转移到其他组织时发生的组织 - 组织相互作用。这些系统能够模拟人体新陈代谢，包括前药转化为其有效代谢物以及随后的治疗作用和毒副作用。由于人体内的组织 - 组织相互作用在决定新药物的成功与否方面起着重要作用，多器官微器件的开发和使用为改进药物研发过程提供了机会。其目标是在药物进入昂贵的临床试验阶段之前更准确地预测潜在的毒副作用，并评估疗效和剂量反应。多器官微器件还可能通过提供一个在人体新陈代谢背景下（而非动物模型）进行测试的平台，有助于开发新的治疗策略。此外，当使用人体活检样本进行操作时，这些器件可能成为开发个体化医疗的途径。在此，我们回顾了一些研究，在这些研究中多器官微器件得以开发和使用，其方式展示了这些器件的能力如何为药物作用的研究提供独特的机会。我们还讨论了多器官微器件开发中固有的挑战。其中包括如何设计这些器件，以及如何制造出能高度真实地模拟人体新陈代谢的器件。由于单器官器件是组织的测试平台，这些组织之后可在多器官器件中与其他组织相结合，我们也会在讨论中适当地提及单器官器件。
Multi-organ microdevices can mimic tissue-tissue interactions that occur as a result of metabolite travel from one tissue to other tissues in vitro. These systems are capable of simulating human metabolism, including the conversion of a pro-drug to its effective metabolite as well as its subsequent therapeutic actions and toxic side effects. Since tissue-tissue interactions in the human body can play a significant role in determining the success of new pharmaceuticals, the development and use of multi-organ microdevices presents an opportunity to improve the drug development process. The goals are to predict potential toxic side effects with higher accuracy before a drug enters the expensive phase of clinical trials as well as to estimate efficacy and dose response. Multi-organ microdevices also have the potential to aid in the development of new therapeutic strategies by providing a platform for testing in the context of human metabolism (as opposed to animal models). Further, when operated with human biopsy samples, the devices could be a gateway for the development of individualized medicine. Here we review studies in which multi-organ microdevices have been developed and used in a ways that demonstrate how the devices’ capabilities can present unique opportunities for the study of drug action. We also discuss the challenges that are inherent in the development of multi-organ microdevices. Among these are how to design the devices, and how to create devices that mimic the human metabolism with high authenticity. Since single organ devices are testing platforms for tissues that can later be combined with other tissues within multi-organ devices, we will also mention single organ devices where appropriate in the discussion.
登录
查看更多内容
影响因子：
4.1
作者：
Esch, Mandy B.;Post, David J.;Stokol, Tracy
通讯作者：
Stokol, Tracy
DOI：
10.1016/j.ejpb.2012.10.003
发表时间：
2013-04-01
影响因子：
4.9
作者：
Antunes, Filipa;Andrade, Fernanda;Sarmento, Bruno
通讯作者：
Sarmento, Bruno
影响因子：
2.9
作者：
Das, M;Molnar, P;Hickman, JJ
通讯作者：
Hickman, JJ
影响因子：
2.2
作者：
DiMasi, Joseph A.;Grabowski, Henry G.
通讯作者：
Grabowski, Henry G.
DOI：
10.1016/j.msec.2003.12.002
发表时间：
2004-04-01
期刊：
MATERIALS SCIENCE & ENGINEERING C-BIOMIMETIC AND SUPRAMOLECULAR SYSTEMS
影响因子：
--
作者：
Choi, SH;Fukuda, O;Sakai, Y
通讯作者：
Sakai, Y