Chemical Engineering Department, Polytechnique Montreal, Canada; Institute of Biomedical Engineering, Polytechnique Montreal, Canada.
Department of Surgery, Division of Orthopaedic Surgery, McGill University, Canada.
Biomater Adv. 2022 Mar;134:112566. doi: 10.1016/j.msec.2021.112566. Epub 2021 Nov 29.
Metastatic cancers can be highly heterogeneous, show large patient variability and are typically hard to treat due to chemoresistance. Personalized therapies are therefore needed to suppress tumor growth and enhance patient's quality of life. Identifying appropriate patient-specific therapies remains a challenge though, due mainly to non-physiological in vitro culture systems. Therefore, more complex and physiological in vitro human cancer microenvironment tools could drastically aid in development of new therapies. We developed a plasma-modified, electro-spun 3D scaffold (PP-3D-S) that can mimic the human cancer microenvironment for customized-cancer therapeutic screening. The PP-3D-S was characterized for optimal plasma-modifying treatment and scaffolds morphology including fiber diameter and pore size. PP-3D-S was then seeded with human fibroblasts to mimic a stromal tissue layer; cell adhesion on plasma-modified poly (lactic acid), PLA, electrospun mats vastly exceeded that on untreated controls. The cell-seeded scaffolds were then overlaid with alginate/gelatin-based hydrogel embedded with MDA-MB231 human breast cancer cells, representing a tumor-tissue interface. Among three different plasma treatments, we found that NH plasma promoted the most tumor cell migration to the scaffold surfaces after 7 days of culture. For all treated and non-treated mats, we observed a significant difference in tumor cell migration between small-sized and either medium- or large-sized scaffolds. In addition, we found that the PP-3D-S was highly comparable to the standard Matrigel® migration assays in two different sets of doxorubicin screening experiments, where 75% reduction in migration was achieved with 0.5 μM doxorubicin for both systems. Taken together, our data indicate that PP-3D-S is an effective, low-cost, and easy-to-use alternate 3D tumor migration model which may be suitable as a physiological drug screening tool for personalized medicine against metastatic cancers.
转移性癌症可能高度异质，表现出较大的患者变异性，并且由于化疗耐药性通常难以治疗。因此，需要个性化治疗来抑制肿瘤生长并提高患者的生活质量。然而，由于非生理的体外培养系统，确定合适的患者特异性治疗方法仍然是一个挑战。因此，更复杂和生理的体外人类癌症微环境工具可以极大地帮助开发新的治疗方法。我们开发了一种等离子改性的、电纺的 3D 支架（PP-3D-S），可以模拟人类癌症微环境，用于定制癌症治疗筛选。对 PP-3D-S 进行了最佳等离子改性处理和支架形态（包括纤维直径和孔径）的特征描述。然后将 PP-3D-S 接种人成纤维细胞以模拟基质组织层；与未处理对照相比，等离子改性聚乳酸（PLA）电纺垫上的细胞黏附大大增加。然后将细胞接种的支架与含有 MDA-MB231 人乳腺癌细胞的藻酸盐/明胶基水凝胶覆盖，代表肿瘤组织界面。在三种不同的等离子体处理中，我们发现 NH 等离子体在培养 7 天后促进了最多的肿瘤细胞迁移到支架表面。对于所有处理和未处理的垫，我们观察到在小尺寸和中尺寸或大尺寸支架之间，肿瘤细胞迁移存在显著差异。此外，我们发现 PP-3D-S 在两种不同的阿霉素筛选实验中与标准 Matrigel®迁移测定高度可比，在这两种系统中，0.5μM 阿霉素即可实现 75%的迁移减少。总之，我们的数据表明，PP-3D-S 是一种有效、低成本且易于使用的替代 3D 肿瘤迁移模型，可作为针对转移性癌症的个性化药物的生理药物筛选工具。
