State Key Laboratory of Fine Chemicals, Dalian R&D Center for Stem Cell and Tissue Engineering, Dalian University of Technology, Dalian 116024, China.
Regenerative Medicine Center and Stem Cell Clinical Research Center, First Affiliated Hospital of Dalian Medical University, Dalian 116024, China.
Int J Biol Macromol. 2019 Jun 1;130:166-176. doi: 10.1016/j.ijbiomac.2019.02.136. Epub 2019 Feb 23.
Potential anti-cancer drugs are frequently of low efficacy in clinics due to the lack of predictive models or the insufficient employment of existing preclinical test systems. Three-dimensional (3D) in vitro engineered tumor models can better predict the efficacy of novel drugs by reproducing the in vivo tumor microenvironment. In this study, three sources of scaffolds (decellularized lung scaffold, chitosan/gelatin scaffold, and poly-L-lactic acid scaffold) incorporated with breast cancer cells (MCF-7, 4T1) were bioengineered as a platform to study in vitro solid tumor development. The good biocompatibility of three scaffolds favored cell growth and proliferation. Cells in 3D scaffolds were less sensitive to chemotherapy and exhibited characteristics of higher malignancy compared to their 2D counterparts. The expression of breast cancer biomarkers in MCF-7 cells markedly up-regulated in 3D scaffolds in comparison with those in 2D cultures. Cells grown in 3D scaffolds were found to be more tumorigenic and angiogenic in BABL/c mice xenografts than cells grown from monolayers. The results demonstrate that 3D engineered tumor model can better mimic in vivo tumor and can serve as a more appropriate platform for the study and screening of novel cancer therapeutics.
由于缺乏预测模型或对现有临床前测试系统的利用不足,潜在的抗癌药物在临床上往往疗效不佳。三维(3D)体外工程肿瘤模型通过重现体内肿瘤微环境,可以更好地预测新型药物的疗效。在这项研究中,三种支架(脱细胞肺支架、壳聚糖/明胶支架和聚 L-乳酸支架)与乳腺癌细胞(MCF-7、4T1)结合,被生物工程化为一个平台,用于研究体外实体瘤的发展。三种支架具有良好的生物相容性,有利于细胞的生长和增殖。与二维培养物相比,三维支架中的细胞对化疗的敏感性较低,表现出更高恶性的特征。与二维培养物相比,MCF-7 细胞在 3D 支架中的乳腺癌生物标志物表达明显上调。在 BABL/c 小鼠异种移植中,与从单层细胞生长的细胞相比,在 3D 支架中生长的细胞具有更强的致瘤性和血管生成能力。研究结果表明,3D 工程肿瘤模型可以更好地模拟体内肿瘤,并且可以作为研究和筛选新型癌症治疗方法的更合适的平台。