School of Mechanical Engineering, Sungkyunkwan University, Suwon 16419, Korea.
Department of Biomedical Engineering, Sungkyunkwan University, Suwon 16419, Korea.
Int J Mol Sci. 2020 Apr 23;21(8):2993. doi: 10.3390/ijms21082993.
An in vitro screening system for anti-cancer drugs cannot exactly reflect the efficacy of drugs in vivo, without mimicking the tumour microenvironment (TME), which comprises cancer cells interacting with blood vessels and fibroblasts. Additionally, the tumour size should be controlled to obtain reliable and quantitative drug responses. Herein, we report a bioprinting method for recapitulating the TME with a controllable spheroid size. The TME was constructed by printing a blood vessel layer consisting of fibroblasts and endothelial cells in gelatine, alginate, and fibrinogen, followed by seeding multicellular tumour spheroids (MCTSs) of glioblastoma cells (U87 MG) onto the blood vessel layer. Under MCTSs, sprouts of blood vessels were generated and surrounding MCTSs thereby increasing the spheroid size. The combined treatment involving the anti-cancer drug temozolomide (TMZ) and the angiogenic inhibitor sunitinib was more effective than TMZ alone for MCTSs surrounded by blood vessels, which indicates the feasibility of the TME for in vitro testing of drug efficacy. These results suggest that the bioprinted vascularized tumour is highly useful for understanding tumour biology, as well as for in vitro drug testing.
一种用于抗癌药物的体外筛选系统，如果不能模拟肿瘤微环境（TME），即包含与血管和成纤维细胞相互作用的癌细胞，就无法准确反映药物在体内的疗效。此外，应控制肿瘤大小以获得可靠和定量的药物反应。在此，我们报告了一种生物打印方法，用于重现具有可控球体大小的 TME。通过在明胶、海藻酸钠和纤维蛋白原中打印包含成纤维细胞和内皮细胞的血管层，然后将多细胞肿瘤球体（U87MG 胶质母细胞瘤细胞）接种到血管层上，构建了 TME。在 MCTS 下，血管芽生成并包围 MCTS，从而增加了球体的大小。与血管周围的 MCTS 联合使用抗癌药物替莫唑胺（TMZ）和血管生成抑制剂舒尼替尼的联合治疗比单独使用 TMZ 更有效，这表明 TME 可用于体外药物疗效测试。这些结果表明，生物打印的血管化肿瘤对于理解肿瘤生物学以及体外药物测试非常有用。
