CNR-ISTEC, Institute of Science and Technology for Ceramics, National Research Council of Italy, 48018, Faenza, RA, Italy.
Sci Rep. 2020 Dec 18;10(1):22294. doi: 10.1038/s41598-020-79448-y.
The failure of the osteosarcoma conventional therapies leads to the growing need for novel therapeutic strategies. The lack of specificity for the Cancer Stem Cells (CSCs) population has been recently identified as the main limitation in the current therapies. Moreover, the traditional two-dimensional (2D) in vitro models, employed in the drug testing and screening as well as in the study of cell and molecular biology, are affected by a poor in vitro-in vivo translation ability. To overcome these limitations, this work provides two tumour engineering approaches as new tools to address osteosarcoma and improve therapy outcomes. In detail, two different hydroxyapatite-based bone-mimicking scaffolds were used to recapitulate aspects of the in vivo tumour microenvironment, focusing on CSCs niche. The biological performance of human osteosarcoma cell lines (MG63 and SAOS-2) and enriched-CSCs were deeply analysed in these complex cell culture models. The results highlight the fundamental role of the tumour microenvironment proving the mimicry of osteosarcoma stem cell niche by the use of CSCs together with the biomimetic scaffolds, compared to conventional 2D culture systems. These advanced 3D cell culture in vitro tumour models could improve the predictivity of preclinical studies and strongly enhance the clinical translation.
骨肉瘤常规疗法的失败导致人们对新型治疗策略的需求不断增长。最近发现，癌症干细胞（CSC）群体缺乏特异性是当前疗法的主要限制。此外，传统的二维（2D）体外模型在药物测试和筛选以及细胞和分子生物学研究中被用于研究，其在体外到体内的转化能力较差。为了克服这些限制，这项工作提供了两种肿瘤工程方法，作为解决骨肉瘤和改善治疗效果的新工具。具体来说，使用了两种不同的基于羟基磷灰石的仿生骨支架来再现体内肿瘤微环境的各个方面，重点是 CSC 生态位。在这些复杂的细胞培养模型中，深入分析了人骨肉瘤细胞系（MG63 和 SAOS-2）和富集的 CSC 的生物学性能。结果突出了肿瘤微环境的基本作用，证明了使用 CSC 结合仿生支架可以模拟骨肉瘤干细胞生态位，与传统的 2D 培养系统相比。这些先进的 3D 体外肿瘤细胞培养模型可以提高临床前研究的预测性，并大大增强临床转化。
