Is it Time for Reviewer 3 to Request Human Organ Chip Experiments Instead of Animal Validation Studies?

Is it Time for Reviewer 3 to Request Human Organ Chip Experiments Instead of Animal Validation Studies?
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DOI:
10.1002/advs.202002030
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发表时间:
2020-11
期刊:
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
影响因子:
--
通讯作者:
Ingber DE
Ingber DE
中科院分区:
其他
文献类型:
--
作者:
Ingber DE

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在过去的世纪里,科学论文和资助申请的评审者要求从动物研究中获得实验数据,以验证体外结果的生理相关性。与此同时,制药研究人员和监管机构认识到,临床前动物模型的结果往往无法预测人类的药物反应。本进展报告回顾了人体器官芯片(器官芯片)微流控培养技术的最新进展,包括单器官芯片和流体耦合的人体“芯片上的身体”平台,这些平台证明了它们能够重现人体生理学和疾病状态,以及人类患者对临床相关药物药代动力学暴露的反应,比其他体外模型或动物研究具有更高的保真度。这些发现提出了一个问题,即继续要求动物试验结果用于出版或资助是否仍然具有科学或伦理意义,以及是否更生理相关的人体器官芯片模型可能更好地服务于这一目的。本文在该领域历史的背景下讨论了这个问题,并讨论了器官芯片方法与动物模型相比的优点和缺点,这些优点和缺点应该被更广泛的研究界考虑。本文综述了人体器官芯片微流控培养技术的最新进展,表明它可以模拟人体生理,疾病状态和对药物的反应,比一些动物模型更准确。这就提出了一个问题,即出版物和赠款的审查员是否应该考虑要求进行人体器官芯片研究,以代替动物试验。
For the past century, experimental data obtained from animal studies have been required by reviewers of scientific articles and grant applications to validate the physiological relevance of in vitro results. At the same time, pharmaceutical researchers and regulatory agencies recognize that results from preclinical animal models frequently fail to predict drug responses in humans. This Progress Report reviews recent advances in human organ‐on‐a‐chip (Organ Chip) microfluidic culture technology, both with single Organ Chips and fluidically coupled human “Body‐on‐Chips” platforms, which demonstrate their ability to recapitulate human physiology and disease states, as well as human patient responses to clinically relevant drug pharmacokinetic exposures, with higher fidelity than other in vitro models or animal studies. These findings raise the question of whether continuing to require results of animal testing for publication or grant funding still makes scientific or ethical sense, and if more physiologically relevant human Organ Chip models might better serve this purpose. This issue is addressed in this article in context of the history of the field, and advantages and disadvantages of Organ Chip approaches versus animal models are discussed that should be considered by the wider research community. This article reviews recent advances with human Organ Chip microfluidic culture technology showing that it can mimic human physiology, disease states, and responses to drugs with higher accuracy than some animal models. This raises the question whether it might be time for reviewers of publications and grants to consider requesting human Organ Chip studies in lieu of animal testing.
发行者校正:人类胰岛和肝球体的功能耦合在片上:迈向一种新型的人体外体2型糖尿病模型。
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