Mammalian Cell Culture Lab, Premas Biotech Pvt Ltd., Imt Manesar, Gurgaon 122050, India.
Oncol Rep. 2023 Jan;49(1). doi: 10.3892/or.2022.8439. Epub 2022 Nov 11.
Cancer can be fatal if it is not treated in a timely manner; therefore, there is a high demand for more specific oncology drugs. Unfortunately, drugs showing positive responses on a two‑dimensional (2D) culture platform do not often show the same effect in clinical trials. Therefore, three‑dimensional (3D) culture platforms are garnering attention since they more closely mimic the tumor microenvironment (TME). The TME stimulates metastasis and drug resistance, and serves an essential role in tumor formation. An accurate understanding of tumor‑stroma interactions is undoubtedly required to improve the response of patients to therapeutic strategies, and cancer therapeutic strategies that do not account for the stroma are considered inadequate. It should be noted that 3D monoculture systems do not completely mimic the TME since other cells in the 3D culture are missing, such as fibroblast or endothelial cells, which are essential components of the stroma; therefore, it is essential to develop advanced 3D culture systems. The present study aimed to develop a versatile triculture model that mimics the native TME; therefore, it could aid in high‑throughput screening of chemotherapeutic drugs against cancer by evaluating their effects on tumor progression and cell cytotoxicity. The present study demonstrated the use of the AXTEX‑4D™ platform in developing triculture tissueoids composed of MCF‑7, human umbilical vein endothelial cells and MRC5 cells, and compared it with a 3D monoculture model (MCF‑7) and a 2D culture model. The triculture model was validated for proliferation, ECM markers and T‑cell infiltration by confocal microscopy. Alamar Blue assay demonstrated that triculture tissueoids exhibited higher drug resistance than the other two models, thus demonstrating their use in the screening of oncology drugs.
如果癌症不能及时治疗，可能会致命；因此，对更具针对性的肿瘤药物有很高的需求。不幸的是，在二维（2D）培养平台上显示出积极反应的药物在临床试验中往往不会显示出相同的效果。因此，三维（3D）培养平台受到关注，因为它们更能模拟肿瘤微环境（TME）。TME 会刺激转移和耐药性，并在肿瘤形成中起着至关重要的作用。准确了解肿瘤-基质相互作用无疑是提高患者对治疗策略反应的必要条件，而不考虑基质的癌症治疗策略被认为是不充分的。需要注意的是，3D 单细胞培养系统并不能完全模拟 TME，因为 3D 培养中缺少其他细胞，如成纤维细胞或内皮细胞，它们是基质的重要组成部分；因此，开发先进的 3D 培养系统至关重要。本研究旨在开发一种多功能的三培养模型，以模拟天然的 TME；因此，它可以通过评估其对肿瘤进展和细胞细胞毒性的影响，有助于高通量筛选抗癌化疗药物。本研究展示了使用 AXTEX-4D™ 平台开发由 MCF-7、人脐静脉内皮细胞和 MRC5 细胞组成的三培养组织体，并将其与 3D 单细胞培养模型（MCF-7）和 2D 培养模型进行了比较。通过共聚焦显微镜验证了三培养模型的增殖、细胞外基质标志物和 T 细胞浸润情况。Alamar Blue 检测结果表明，三培养组织体的耐药性高于其他两种模型，从而证明了它们在肿瘤药物筛选中的应用。
