Prodanov Ljupcho, Jindal Rohit, Bale Shyam Sundhar, Hegde Manjunath, McCarty William J, Golberg Inna, Bhushan Abhinav, Yarmush Martin L, Usta Osman Berk
Center for Engineering in Medicine at Massachusetts General Hospital, Harvard Medical School and Shriners Hospital for Children, 51 Blossom St., Boston, 02144, Massachusetts.
Department of Biomedical Engineering, Rutgers University, 599 Taylor Rd., Piscataway, 08854, New Jersey.
Biotechnol Bioeng. 2016 Jan;113(1):241-6. doi: 10.1002/bit.25700. Epub 2015 Aug 26.
The development of long-term human organotypic liver-on-a-chip models for successful prediction of toxic response is one of the most important and urgent goals of the NIH/DARPA's initiative to replicate and replace chronic and acute drug testing in animals. For this purpose, we developed a microfluidic chip that consists of two microfluidic chambers separated by a porous membrane. The aim of this communication is to demonstrate the recapitulation of a liver sinusoid-on-a-chip, using human cells only for a period of 28 days. Using a step-by-step method for building a 3D microtissue on-a-chip, we demonstrate that an organotypic in vitro model that reassembles the liver sinusoid microarchitecture can be maintained successfully for a period of 28 days. In addition, higher albumin synthesis (synthetic) and urea excretion (detoxification) were observed under flow compared to static cultures. This human liver-on-a-chip should be further evaluated in drug-related studies.
开发长期人体器官芯片型肝脏模型以成功预测毒性反应，是美国国立卫生研究院/国防高级研究计划局旨在复制和取代动物慢性和急性药物测试的倡议中最重要且最紧迫的目标之一。为此，我们开发了一种微流控芯片，它由两个由多孔膜分隔的微流控腔室组成。本通讯的目的是展示仅使用人类细胞构建的芯片型肝血窦在28天内的重现情况。通过一种在芯片上构建3D微组织的逐步方法，我们证明了一种能够重新组装肝血窦微结构的体外器官型模型可以成功维持28天。此外，与静态培养相比，流动条件下观察到更高的白蛋白合成（合成功能）和尿素排泄（解毒功能）。这种人体芯片肝脏模型应在药物相关研究中进一步评估。
