Biology-inspired microphysiological system approaches to solve the prediction dilemma of substance testing.
Biology-inspired microphysiological system approaches to solve the prediction dilemma of substance testing.
复制标题
DOI：
10.14573/altex.1603161
复制
发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Roth A
中科院分区：
文献类型：
--
作者：
Marx U;Andersson TB;Bahinski A;Beilmann M;Beken S;Cassee FR;Cirit M;Daneshian M;Fitzpatrick S;Frey O;Gaertner C;Giese C;Griffith L;Hartung T;Heringa MB;Hoeng J;de Jong WH;Kojima H;Kuehnl J;Leist M;Luch A;Maschmeyer I;Sakharov D;Sips AJ;Steger-Hartmann T;Tagle DA;Tonevitsky A;Tralau T;Tsyb S;van de Stolpe A;Vandebriel R;Vulto P;Wang J;Wiest J;Rodenburg M;Roth A
最近出现的微生理系统-微流体仿生装置，渴望模仿人体组织，器官和体外循环的生物学-被设想为实现药物开发的全球范式转变。最近，美国政府的一项非凡倡议以及欧洲和亚洲的各种专门研究计划导致了基于微生理系统的人类单器官和多器官工程的第一个前沿成就。期望在此基础上建立的测试系统将模拟各种疾病阶段，并在临床测试之前预测毒性、免疫原性、ADME特征和治疗功效。因此，这项技术可能会对未来药物的开发方式产生重大影响。此外，基于微生理系统的测定可能会彻底改变我们目前的全球计划，优先考虑任何新物质的危害特性，例如，在农业，食品，生态系统或化妆品中，从而取代目前使用的实验室动物模型。来自学术界、工业界和监管机构的35位专家在此介绍了一次密集研讨会（2015年6月在德国柏林举行）的成果。他们根据行业需求回顾了当今可用的微生理系统的现状，并评估了在药物开发周期中具有适用潜力的各种方法。提出了可行的技术解决方案，以达到体外人类生物学的下一个水平。此外，重点介绍了关键的器官芯片案例研究以及各种国家和国际项目。最后，概述了未来的路线图，以便在全球范围内进行更具预测性和监管接受的物质检测。
The recent advent of microphysiological systems – microfluidic biomimetic devices that aspire to emulate the biology of human tissues, organs and circulation in vitro – is envisaged to enable a global paradigm shift in drug development. An extraordinary US governmental initiative and various dedicated research programs in Europe and Asia have led recently to the first cutting-edge achievements of human single-organ and multi-organ engineering based on microphysiological systems. The expectation is that test systems established on this basis would model various disease stages, and predict toxicity, immunogenicity, ADME profiles and treatment efficacy prior to clinical testing. Consequently, this technology could significantly affect the way drug substances are developed in the future. Furthermore, microphysiological system-based assays may revolutionize our current global programs of prioritization of hazard characterization for any new substances to be used, for example, in agriculture, food, ecosystems or cosmetics, thus, replacing laboratory animal models used currently. Thirty-five experts from academia, industry and regulatory bodies present here the results of an intensive workshop (held in June 2015, Berlin, Germany). They review the status quo of microphysiological systems available today against industry needs, and assess the broad variety of approaches with fit-for-purpose potential in the drug development cycle. Feasible technical solutions to reach the next levels of human biology in vitro are proposed. Furthermore, key organ-on-a-chip case studies, as well as various national and international programs are highlighted. Finally, a roadmap into the future is outlined, to allow for more predictive and regulatory-accepted substance testing on a global scale.