McMillan Kay S, McCluskey Anthony G, Sorensen Annette, Boyd Marie, Zagnoni Michele
Centre for Microsystems and Photonics, Electronic and Electrical Engineering, University of Strathclyde, Glasgow, G1 1XW, UK.
Analyst. 2016 Jan 7;141(1):100-10. doi: 10.1039/c5an01382h. Epub 2015 Oct 12.
A major limitation with current in vitro technologies for testing anti-cancer therapies at the pre-clinical level is the use of 2D cell culture models which provide a poor reflection of the tumour physiology in vivo. Three dimensional cell culture models, such as the multicellular spheroid, provide instead a more accurate representation. However, existing spheroid-based assessment methods are generally labour-intensive and low-throughput. Emulsion based technologies offer enhanced mechanical stability during multicellular tumour spheroid formation and culture and are scalable to enable higher-throughput assays. The aim of this study was to investigate the characteristics of emulsion-based techniques for the formation and long term culture of multicellular UVW glioma cancer spheroids and apply these findings to assess the cytotoxic effect of radiation on spheroids. Our results showed that spheroids formed within emulsions had similar morphological and growth characteristics to those formed using traditional methods. Furthermore, we have identified the effects produced on the proliferative state of the spheroids due to the compartmentalised nature of the emulsions and applied this for mimicking tumour growth and tumour quiescence. Finally, proof of concept results are shown to demonstrate the scalability potential of the technology for developing high-throughput screening assays.
当前用于临床前水平测试抗癌疗法的体外技术的一个主要局限是使用二维细胞培养模型,这种模型不能很好地反映体内肿瘤生理学。相反,三维细胞培养模型,如多细胞球体,能提供更准确的表征。然而,现有的基于球体的评估方法通常劳动强度大且通量低。基于乳液的技术在多细胞肿瘤球体形成和培养过程中提供了增强的机械稳定性,并且具有可扩展性以实现更高通量的检测。本研究的目的是研究基于乳液的技术在多细胞UVW神经胶质瘤癌球体形成和长期培养方面的特性,并将这些发现应用于评估辐射对球体的细胞毒性作用。我们的结果表明,在乳液中形成的球体与使用传统方法形成的球体具有相似的形态和生长特征。此外,我们已经确定了由于乳液的分隔性质对球体增殖状态产生的影响,并将其应用于模拟肿瘤生长和肿瘤静止。最后,概念验证结果表明了该技术在开发高通量筛选检测方面的可扩展性潜力。