Coaxial 3D bioprinting of self-assembled multicellular heterogeneous tumor fibers.
Coaxial 3D bioprinting of self-assembled multicellular heterogeneous tumor fibers.
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DOI：
10.1038/s41598-017-01581-y
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发表时间：
2017-05-03
影响因子：
4.6
通讯作者：
Xu T
中科院分区：
文献类型：
--
作者：
Dai X;Liu L;Ouyang J;Li X;Zhang X;Lan Q;Xu T
在体外已经实现了用载有细胞的生物材料三维（3D）生物打印活体结构，然而，一些细胞-细胞相互作用受到现有水凝胶的限制。为了更好地模拟肿瘤微环境，自组装的多细胞异质性脑肿瘤纤维已经通过定制的同轴挤出3D生物打印系统制造，具有高活力，增殖活性和有效的肿瘤-基质相互作用。其中，为了进一步验证肿瘤细胞和基质MSC之间的充分相互作用，使用了含有用“LOXP-STOP-LOXP-RFP”基因转染的GSC和用“CRE重组酶”基因转染的MSC的CRE-LOXP开关基因系统。结果显示，肿瘤-基质细胞相互作用并融合，RFP的转录分别高于2D培养模型和细胞直接混合到藻酸盐中的对照组。共聚焦显微镜下观察到RFP仅在细胞纤维中表达，而对照组中未观察到。总之，同轴3D生物打印的多细胞自组装异质肿瘤组织样纤维为体外研究肿瘤微环境，特别是肿瘤-基质相互作用提供了优选的3D模型。
Three-dimensional (3D) bioprinting of living structures with cell-laden biomaterials has been achieved in vitro, however, some cell-cell interactions are limited by the existing hydrogel. To better mimic tumor microenvironment, self-assembled multicellular heterogeneous brain tumor fibers have been fabricated by a custom-made coaxial extrusion 3D bioprinting system, with high viability, proliferative activity and efficient tumor-stromal interactions. Therein, in order to further verify the sufficient interactions between tumor cells and stroma MSCs, CRE-LOXP switch gene system which contained GSCs transfected with “LOXP-STOP-LOXP-RFP” genes and MSCs transfected with “CRE recombinase” gene was used. Results showed that tumor-stroma cells interacted with each other and fused, the transcription of RFP was higher than that of 2D culture model and control group with cells mixed directly into alginate, respectively. RFP expression was observed only in the cell fibers but not in the control group under confocal microscope. In conclusion, coaxial 3D bioprinted multicellular self-assembled heterogeneous tumor tissue-like fibers provided preferable 3D models for studying tumor microenvironment in vitro, especially for tumor-stromal interactions.