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用于肿瘤细胞药物筛选和递送的芯片器官平台:一项系统综述

Organ-on-a-Chip Platforms for Drug Screening and Delivery in Tumor Cells: A Systematic Review.

作者信息

Gonçalves Inês M, Carvalho Violeta, Rodrigues Raquel O, Pinho Diana, Teixeira Senhorinha F C F, Moita Ana, Hori Takeshi, Kaji Hirokazu, Lima Rui, Minas Graça

机构信息

METRICS, University of Minho, Alameda da Universidade, 4800-058 Guimarães, Portugal.

IN+-Center for Innovation, Technology and Policy Research, Instituto Superior Técnico, Universidade de Lisboa, Avenida Rovisco Pais, 1049-001 Lisboa, Portugal.

出版信息

Cancers (Basel). 2022 Feb 13;14(4):935. doi: 10.3390/cancers14040935.

Abstract

The development of cancer models that rectify the simplicity of monolayer or static cell cultures physiologic microenvironment and, at the same time, replicate the human system more accurately than animal models has been a challenge in biomedical research. Organ-on-a-chip (OoC) devices are a solution that has been explored over the last decade. The combination of microfluidics and cell culture allows the design of a dynamic microenvironment suitable for the evaluation of treatments' efficacy and effects, closer to the response observed in patients. This systematic review sums the studies from the last decade, where OoC with cancer cell cultures were used for drug screening assays. The studies were selected from three databases and analyzed following the research guidelines for systematic reviews proposed by PRISMA. In the selected studies, several types of cancer cells were evaluated, and the majority of treatments tested were standard chemotherapeutic drugs. Some studies reported higher drug resistance of the cultures on the OoC devices than on 2D cultures, which indicates the better resemblance to in vivo conditions of the former. Several studies also included the replication of the microvasculature or the combination of different cell cultures. The presence of vasculature can influence positively or negatively the drug efficacy since it contributes to a greater diffusion of the drug and also oxygen and nutrients. Co-cultures with liver cells contributed to the evaluation of the systemic toxicity of some drugs metabolites. Nevertheless, few studies used patient cells for the drug screening assays.

摘要

开发能够纠正单层或静态细胞培养生理微环境简单性,同时比动物模型更准确地复制人体系统的癌症模型,一直是生物医学研究中的一项挑战。芯片器官(OoC)装置是过去十年中探索的一种解决方案。微流体技术与细胞培养的结合使得能够设计出一种动态微环境,适合评估治疗效果,更接近在患者身上观察到的反应。本系统综述总结了过去十年中使用癌细胞培养的芯片器官进行药物筛选试验的研究。这些研究从三个数据库中选取,并按照PRISMA提出的系统综述研究指南进行分析。在所选研究中,评估了几种类型的癌细胞,测试的大多数治疗方法是标准化疗药物。一些研究报告称,芯片器官装置上的培养物比二维培养物具有更高的耐药性,这表明前者与体内条件更相似。几项研究还包括微血管的复制或不同细胞培养的组合。血管的存在可能对药物疗效产生积极或消极影响,因为它有助于药物以及氧气和营养物质的更广泛扩散。与肝细胞的共培养有助于评估某些药物代谢物的全身毒性。然而,很少有研究使用患者细胞进行药物筛选试验。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61af/8870045/82f5aac991b1/cancers-14-00935-g001.jpg

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