Microengineered cell and tissue systems for drug screening and toxicology applications: Evolution of in-vitro liver technologies.
Microengineered cell and tissue systems for drug screening and toxicology applications: Evolution of in-vitro liver technologies.
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DOI：
10.1142/s2339547815300012
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发表时间：
2015-03
期刊：
影响因子：
--
通讯作者：
Yarmush ML
中科院分区：
文献类型：
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作者：
Usta OB;McCarty WJ;Bale S;Hegde M;Jindal R;Bhushan A;Golberg I;Yarmush ML
肝脏执行许多关键功能，其中最突出的是作为身体的代谢中心。出于这个原因，肝脏是许多研究的焦点，旨在了解生物体对内源性和外源性挑战的毒理学反应。由于如此多的药物失败涉及直接的肝毒性或来自肝产生的代谢物的其他器官毒性，因此制药工业一直在寻求上级的预测性体外模型，其可以在有问题的候选药物产生主要的开发成本之前，并且当然在它们被发布给公众之前，更快速和有效地识别出有问题的候选药物。在这篇广泛的综述中，我们对体外肝脏技术进行了调查和批判性比较，沿着广泛的范围，但重点是目前重新推动开发“器官芯片”。从这次审查中得出的一组突出结论是，虽然最近的大量工作已经引导该领域对所需内容有了更全面的了解，但该领域仍然非常需要几个关键进展，包括建立标准表征方法，模拟体内细胞环境的增强技术，以及更好的计算方法来弥合体外和体内结果之间的差距。
The liver performs many key functions, the most prominent of which is serving as the metabolic hub of the body. For this reason, the liver is the focal point of many investigations aimed at understanding an organism’s toxicological response to endogenous and exogenous challenges. Because so many drug failures have involved direct liver toxicity or other organ toxicity from liver generated metabolites, the pharmaceutical industry has constantly sought superior, predictive in-vitro models that can more quickly and efficiently identify problematic drug candidates before they incur major development costs, and certainly before they are released to the public. In this broad review, we present a survey and critical comparison of in-vitro liver technologies along a broad spectrum, but focus on the current renewed push to develop “organs-on-a-chip”. One prominent set of conclusions from this review is that while a large body of recent work has steered the field towards an ever more comprehensive understanding of what is needed, the field remains in great need of several key advances, including establishment of standard characterization methods, enhanced technologies that mimic the in-vivo cellular environment, and better computational approaches to bridge the gap between the in-vitro and in-vivo results.