He Jiachen, Chen Chichi, Chen Liang, Cheng Ruoyu, Sun Jie, Liu Xingzhi, Wang Lin, Zhu Can, Hu Sihan, Xue Yuan, Lu Jian, Yang Huiling, Cui Wenguo, Shi Qin
Department of Orthopedics, The First Affiliated Hospital of Soochow University, Orthopedic Institute of Soochow University, 899 Pinghai Road, Suzhou, Jiangsu 215031, China.
National Clinical Research Center for Hematologic Diseases, The First Affiliated Hospital of Soochow University, 899 Pinghai Road, Suzhou, Jiangsu 215031, China.
Research (Wash D C). 2022 Feb 7;2022:9809763. doi: 10.34133/2022/9809763. eCollection 2022.
A two-dimensional (2D) cell culture-based model is widely applied to study tumorigenic mechanisms and drug screening. However, it cannot authentically simulate the three-dimensional (3D) microenvironment of solid tumors and provide reliable and predictable data in response to , thus leading to the research illusions and failure of drug screening. In this study, honeycomb-like gelatin methacryloyl (GelMA) hydrogel microspheres are developed by synchronous photocrosslinking microfluidic technique to construct a 3D model of osteosarcoma. The study shows that osteosarcoma cells (K7M2) cultured in 3D GelMA microspheres have stronger tumorous stemness, proliferation and migration abilities, more osteoclastogenetic ability, and resistance to chemotherapeutic drugs (DOX) than that of cells in 2D cultures. More importantly, the 3D-cultured K7M2 cells show more tumorigenicity in immunologically sound mice, characterized by shorter tumorigenesis time, larger tumor volume, severe bone destruction, and higher mortality. In conclusion, honeycomb-like porous microsphere scaffolds are constructed with uniform structure by microfluidic technology to massively produce tumor cells with original phenotypes. Those microspheres could recapitulate the physiology microenvironment of tumors, maintain cell-cell and cell-extracellular matrix interactions, and thus provide an effective and convenient strategy for tumor pathogenesis and drug screening research.
基于二维（2D）细胞培养的模型被广泛应用于研究肿瘤发生机制和药物筛选。然而，它无法真实模拟实体瘤的三维（3D）微环境，也无法提供针对……的可靠且可预测的数据，从而导致研究错觉和药物筛选失败。在本研究中，通过同步光交联微流控技术制备了蜂窝状甲基丙烯酰化明胶（GelMA）水凝胶微球，以构建骨肉瘤的三维模型。研究表明，与二维培养的细胞相比，在三维GelMA微球中培养的骨肉瘤细胞（K7M2）具有更强的肿瘤干性、增殖和迁移能力、更多的破骨细胞生成能力以及对化疗药物（阿霉素）的抗性。更重要的是，三维培养的K7M2细胞在免疫健全的小鼠中表现出更强的致瘤性，其特征为肿瘤发生时间更短、肿瘤体积更大、严重的骨破坏以及更高的死亡率。总之，利用微流控技术构建了结构均匀的蜂窝状多孔微球支架，以大量产生具有原始表型的肿瘤细胞。这些微球可以重现肿瘤的生理微环境，维持细胞 - 细胞和细胞 - 细胞外基质的相互作用，从而为肿瘤发病机制和药物筛选研究提供一种有效且便捷的策略。
