Institute of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom.
Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, United Kingdom.
PLoS One. 2023 Mar 16;18(3):e0283044. doi: 10.1371/journal.pone.0283044. eCollection 2023.
3D cell culture models of cancer are currently being developed to recapitulate in vivo physiological conditions and to assess therapeutic responses. However, most models failed to incorporate the biochemical and biophysical stimuli from fluid flow. In this study, a three-dimensional scaffold, SeedEZ was applied within the PerfusionPal perfused culture system to investigate how perfusion, and blood-like oxygen delivery influenced breast cancer cell growth and their responses to a commonly used breast cancer drug tamoxifen. Our results showed that breast cancer cells could be maintained over 3 weeks in PerfusionPal with increased cell viability compared to static 3D culture in fully humanised conditions. This platform also supported examining the effect of tamoxifen on breast cancer cell lines and in primary patient-derived breast cancer samples. Future work is warranted to further the adaption for fully humanised assessment of drug effectiveness in a patient personalized approach with the aim to reduce the burden of animal use in cancer research and increase the degree of human pre-clinical data translation to clinic.
目前正在开发癌症的 3D 细胞培养模型,以重现体内生理条件并评估治疗反应。然而,大多数模型未能将流体流动的生化和生物物理刺激纳入其中。在这项研究中,三维支架 SeedEZ 被应用于 PerfusionPal 灌注培养系统中,以研究灌注和类似血液的氧气输送如何影响乳腺癌细胞的生长及其对常用乳腺癌药物他莫昔芬的反应。我们的结果表明,乳腺癌细胞可以在 PerfusionPal 中维持超过 3 周,与完全人源化的静态 3D 培养相比,细胞活力增加。该平台还支持研究他莫昔芬对乳腺癌细胞系和原发性患者来源的乳腺癌样本的影响。未来的工作需要进一步适应,以便在个体化患者评估中全面评估药物的有效性,旨在减少癌症研究中动物使用的负担,并提高人类临床前数据向临床的转化程度。