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首页> 外文期刊>RSC Advances >Integrated heart/cancer on a chip to reproduce the side effects of anti-cancer drugs in vitro
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Integrated heart/cancer on a chip to reproduce the side effects of anti-cancer drugs in vitro

机译：将心脏/癌症整合到芯片上，以在体外再现抗癌药物的副作用

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Pre-clinical animal tests are used to assess drug efficacy and safety, but are limited by factors such as their suitability as a model for humans, robustness, cost, and ethical issues. While an organ-on-a-chip using human cells is promising for recapitulating human physiological conditions, it is highly desirable in investigations of the side effects of drugs to integrate more than one type of tissue using a designed circulatory system. We have developed a microfluidic device—an Integrated Heart/Cancer on a Chip (iHCC)—using human healthy heart cells (hCMs) and liver cancer cells (HepG2) to recapitulate the side effects of an anti-cancer drug, doxorubicin (DXR), to achieve individual cultures of cells from different tissues on a single device with three sets of artificial blood circulation loops, microfabrication technology for micro valves and a pump provides accurate fluid operation. Using improved soft lithography adopting numerical optimization simulation, the microfluidic device was fabricated with on-chip integration of pneumatic valves and a peristaltic micropump establishing precision fluid flow. The iHCC developed allows modelling of the side effects of DXR on heart cells caused by the production of toxic metabolites (doxorubicinol; DXRol) by HepG2 cells and the delivery of DXRol to heart cells via the circulation loop. Our findings open the door towards the development of a “Body-on-a-Chip.”
机译：临床前动物试验用于评估药物的功效和安全性，但受到诸如适合作为人类模型的适用性，健壮性，成本和道德问题等因素的限制。尽管使用人细胞的片上器官有望重现人的生理状况，但是在研究药物的副作用时，使用设计的循环系统整合多种类型的组织是非常需要的。我们已经开发出一种微流控设备-一种集成的心脏/芯片癌（iHCC），它使用人类健康的心脏细胞（hCM）和肝癌细胞（HepG2）来概括抗癌药物阿霉素（DXR）的副作用为了在具有三套人造血液循环回路的单个设备上实现来自不同组织的细胞的单独培养，微阀和泵的微制造技术可提供精确的流体操作。利用改进的软光刻技术，采用数值优化仿真，将微阀装置与气动阀和蠕动微泵的芯片集成集成在一起，从而建立了精确的流体流动。开发的iHCC可以模拟DXR对HepG2细胞产生有毒代谢产物（阿霉素，DXRol）和通过循环环将DXRol递送至心脏细胞所引起的心脏细胞的副作用。我们的发现为“芯片上的身体”的发展打开了大门。

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