Rabionet Marc, Yeste Marc, Puig Teresa, Ciurana Joaquim
New Therapeutic Targets Laboratory (TargetsLab)-Oncology Unit, Department of Medical Sciences, Faculty of Medicine, University of Girona, Emili Grahit 77, 17003 Girona, Spain.
Product, Process and Production Engineering Research Group (GREP), Department of Mechanical Engineering and Industrial Construction, University of Girona, Maria Aurèlia Capmany 61, 17003 Girona, Spain.
Polymers (Basel). 2017 Aug 1;9(8):328. doi: 10.3390/polym9080328.
In vitro cell culture is traditionally performed within two-dimensional (2D) environments, providing a quick and cheap way to study cell properties in a laboratory. However, 2D systems differ from the in vivo environment and may not mimic the physiological cell behavior realistically. For instance, 2D culture models are thought to induce cancer stem cells (CSCs) differentiation, a rare cancer cell subpopulation responsible for tumor initiation and relapse. This fact hinders the development of therapeutic strategies for tumors with a high relapse percentage, such as triple negative breast cancer (TNBC). Thus, three-dimensional (3D) scaffolds have emerged as an attractive alternative to monolayer culture, simulating the extracellular matrix structure and maintaining the differentiation state of cells. In this work, scaffolds were fabricated through electrospinning different poly(ε-caprolactone)-acetone solutions. Poly(ε-caprolactone) (PCL) meshes were seeded with triple negative breast cancer (TNBC) cells and 15% PCL scaffolds displayed significantly ( < 0.05) higher cell proliferation and elongation than the other culture systems. Moreover, cells cultured on PCL scaffolds exhibited higher mammosphere forming capacity and aldehyde dehydrogenase activity than 2D-cultured cells, indicating a breast CSCs enrichment. These results prove the powerful capability of electrospinning technology in terms of poly(ε-caprolactone) nanofibers fabrication. In addition, this study has demonstrated that electrospun 15% PCL scaffolds are suitable tools to culture breast cancer cells in a more physiological way and to expand the niche of breast CSCs. In conclusion, three-dimensional cell culture using PCL scaffolds could be useful to study cancer stem cell behavior and may also trigger the development of new specific targets against such malignant subpopulation.
传统上，体外细胞培养是在二维（2D）环境中进行的，为在实验室研究细胞特性提供了一种快速且廉价的方法。然而，二维系统与体内环境不同，可能无法真实模拟生理细胞行为。例如，二维培养模型被认为会诱导癌症干细胞（CSCs）分化，这是一种罕见的癌细胞亚群，负责肿瘤的起始和复发。这一事实阻碍了针对高复发率肿瘤（如三阴性乳腺癌（TNBC））治疗策略的发展。因此，三维（3D）支架已成为单层培养的一种有吸引力的替代方法，可模拟细胞外基质结构并维持细胞的分化状态。在这项工作中，通过静电纺丝不同的聚（ε-己内酯）-丙酮溶液制备了支架。将三阴性乳腺癌（TNBC）细胞接种到聚（ε-己内酯）（PCL）网片上，15% PCL支架显示出比其他培养系统显著更高（<0.05）的细胞增殖和伸长。此外，在PCL支架上培养的细胞比二维培养的细胞表现出更高的乳腺球形成能力和醛脱氢酶活性，表明富集了乳腺CSCs。这些结果证明了静电纺丝技术在制备聚（ε-己内酯）纳米纤维方面的强大能力。此外，本研究表明，静电纺丝15% PCL支架是以更生理的方式培养乳腺癌细胞并扩大乳腺CSCs生态位的合适工具。总之，使用PCL支架的三维细胞培养可能有助于研究癌症干细胞行为，也可能触发针对这种恶性亚群的新特异性靶点的开发。
