Technische Universität Berlin, Institute of Biotechnology, Department of Medical Biotechnology, Gustav-Meyer-Allee 25, Germany.
Lab Chip. 2013 Sep 21;13(18):3538-47. doi: 10.1039/c3lc50234a.
Current in vitro and animal tests for drug development are failing to emulate the systemic organ complexity of the human body and, therefore, to accurately predict drug toxicity. In this study, we present a multi-organ-chip capable of maintaining 3D tissues derived from cell lines, primary cells and biopsies of various human organs. We designed a multi-organ-chip with co-cultures of human artificial liver microtissues and skin biopsies, each a (1)/100,000 of the biomass of their original human organ counterparts, and have successfully proven its long-term performance. The system supports two different culture modes: i) tissue exposed to the fluid flow, or ii) tissue shielded from the underlying fluid flow by standard Transwell® cultures. Crosstalk between the two tissues was observed in 14-day co-cultures exposed to fluid flow. Applying the same culture mode, liver microtissues showed sensitivity at different molecular levels to the toxic substance troglitazone during a 6-day exposure. Finally, an astonishingly stable long-term performance of the Transwell®-based co-cultures could be observed over a 28-day period. This mode facilitates exposure of skin at the air-liquid interface. Thus, we provide here a potential new tool for systemic substance testing.
目前用于药物开发的体外和动物测试无法模拟人体系统器官的复杂性，因此无法准确预测药物毒性。在本研究中，我们提出了一种多器官芯片，能够维持源自细胞系、原代细胞和各种人体器官活检的 3D 组织。我们设计了一种包含人人工肝微组织和皮肤活检的共培养物的多器官芯片，其生物量分别为人源器官的 1/100,000，并且已经成功证明了其长期性能。该系统支持两种不同的培养模式：i）组织暴露于流体流动中，或 ii）组织通过标准 Transwell®培养物与下面的流体流动隔开。在暴露于流体流动的 14 天共培养物中观察到两种组织之间的串扰。在相同的培养模式下，肝微组织在 6 天暴露于毒性物质曲格列酮时显示出不同分子水平的敏感性。最后，在 28 天的时间内，可以观察到基于 Transwell®的共培养物惊人的稳定长期性能。这种模式有利于空气-液体界面处的皮肤暴露。因此，我们在这里提供了一种用于系统物质测试的潜在新工具。
