Technische Universität Berlin, Institute of Biotechnology, Department Medical Biotechnology, Gustav-Meyer-Allee 25, 13355 Berlin, Germany.
Lab Chip. 2013 Sep 21;13(18):3481-95. doi: 10.1039/c3lc50240f.
Drug-induced liver toxicity dominates the reasons for pharmaceutical product ban, withdrawal or non-approval since the thalidomide disaster in the late-1950s. Hopes to finally solve the liver toxicity test dilemma have recently risen to a historic level based on the latest progress in human microfluidic tissue culture devices. Chip-based human liver equivalents are envisaged to identify liver toxic agents regularly undiscovered by current test procedures at industrial throughput. In this review, we focus on advanced microfluidic microscale liver equivalents, appraising them against the level of architectural and, consequently, functional identity with their human counterpart in vivo. We emphasise the inherent relationship between human liver architecture and its drug-induced injury. Furthermore, we plot the current socio-economic drug development environment against the possible value such systems may add. Finally, we try to sketch a forecast for translational innovations in the field.
自 20 世纪 50 年代末沙利度胺灾难以来，药物性肝毒性主导了药品被禁、撤市或不被批准的原因。最近，基于人类微流控组织培养装置的最新进展，人们终于有望解决肝毒性测试的困境。基于芯片的人类肝脏等效物有望以工业通量定期识别当前测试程序未发现的肝毒性剂。在这篇综述中，我们专注于先进的微流控微尺度肝等效物，根据其与体内人类对应物的结构和功能相似性对其进行评估。我们强调了人类肝脏结构与其药物诱导损伤之间的内在关系。此外，我们将当前的社会经济药物开发环境与这些系统可能带来的价值进行对比。最后，我们尝试对该领域的转化创新进行预测。
