Cantoni Federico, Barbe Laurent, Roy Ananya, Wicher Grzegorz, Simonsson Stina, Forsberg-Nilsson Karin, Tenje Maria
APL Bioeng. 2024 Dec 3;8(4):046113. doi: 10.1063/5.0227135. eCollection 2024 Dec.
The high mortality associated with certain cancers can be attributed to the invasive nature of the tumor cells. Yet, the complexity of studying invasion hinders our understanding of how the tumor spreads. This work presents a microengineered three-dimensional (3D) model for studying cancer cell invasion and interaction with endothelial cells. The model was generated by printing a biomimetic hydrogel scaffold directly on a chip using 2-photon polymerization that simulates the brain's extracellular matrix. The scaffold's geometry was specifically designed to facilitate the growth of a continuous layer of endothelial cells on one side, while also allowing for the introduction of tumor cells on the other side. This arrangement confines the cells spatially and enables microscopy of the cancer cells as they invade the hydrogel scaffold and interact with the endothelial layer. We examined the impact of 3D printing parameters on the hydrogel's physical properties and used patient derived glioblastoma cells to study their effect on cell invasion. Notably, the tumor cells tended to infiltrate faster when an endothelial cell barrier was present. The potential for adjusting the hydrogel scaffold's properties, coupled with the capability for real-time observation of tumor-endothelial cell interactions, offers a platform for studying tumor invasion and tumor-endothelial cell interactions.
某些癌症相关的高死亡率可归因于肿瘤细胞的侵袭性。然而，研究侵袭的复杂性阻碍了我们对肿瘤扩散方式的理解。这项工作提出了一种微工程三维（3D）模型，用于研究癌细胞侵袭以及与内皮细胞的相互作用。该模型是通过使用双光子聚合技术直接在芯片上打印仿生水凝胶支架生成的，该支架模拟了大脑的细胞外基质。支架的几何形状经过专门设计，以便在一侧促进连续内皮细胞层的生长，同时在另一侧也允许引入肿瘤细胞。这种布局在空间上限制了细胞，并能够在癌细胞侵入水凝胶支架并与内皮细胞层相互作用时对其进行显微镜观察。我们研究了3D打印参数对水凝胶物理性质的影响，并使用患者来源的胶质母细胞瘤细胞来研究其对细胞侵袭的作用。值得注意的是，当存在内皮细胞屏障时，肿瘤细胞倾向于更快地浸润。调整水凝胶支架性质的潜力，以及实时观察肿瘤 - 内皮细胞相互作用的能力，为研究肿瘤侵袭和肿瘤 - 内皮细胞相互作用提供了一个平台。
