Villasante Aranzazu, Lopez-Martinez Maria Jose, Quiñonero Gema, Garcia-Lizarribar Andrea, Peng Xiaofeng, Samitier Josep
Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.
Department of Electronic and Biomedical Engineering, University of Barcelona, Barcelona, Spain.
In Vitro Model. 2024 Jan 15;3(1):49-63. doi: 10.1007/s44164-023-00064-x. eCollection 2024 Feb.
Neuroblastoma (NB) is a highly vascularized pediatric tumor arising from undifferentiated neural crest cells early in life, exhibiting both traditional endothelial-cell-driven vasculature and an intriguing alternative vasculature. The alternative vasculature can arise from cancer cells undergoing transdifferentiation into tumor-derived endothelial cells (TEC), a trait associated with drug resistance and tumor relapse. The lack of effective treatments targeting NB vasculature primarily arises from the challenge of establishing predictive in vitro models that faithfully replicate the alternative vasculature phenomenon. In this study, we aim to recreate the intricate vascular system of NB in an in vitro context, encompassing both types of vascularization, by developing a novel neuroblastoma-on-a-chip model. We designed a collagen I/fibrin-based hydrogel closely mirroring NB's physiological composition and tumor stiffness. This biomaterial created a supportive environment for the viability of NB and endothelial cells. Implementing a physiological shear stress value, aligned with the observed range in arteries and capillaries, within the microfluidic chip facilitated the successful development of vessel-like structures and triggered transdifferentiation of NB cells into TECs. The vascularized neuroblastoma-on-a-chip model introduced here presents a promising and complementary strategy to animal-based research with a significant capacity for delving into NB tumor biology and vascular targeting therapy.
The online version contains supplementary material available at 10.1007/s44164-023-00064-x.
神经母细胞瘤（NB）是一种高度血管化的儿科肿瘤，起源于生命早期未分化的神经嵴细胞，具有传统的内皮细胞驱动的脉管系统以及一种有趣的替代性脉管系统。替代性脉管系统可源自经历转分化成为肿瘤衍生内皮细胞（TEC）的癌细胞，这一特征与耐药性和肿瘤复发相关。缺乏针对NB脉管系统的有效治疗方法主要源于建立能够忠实地复制替代性脉管系统现象的预测性体外模型所面临的挑战。在本研究中，我们旨在通过开发一种新型的芯片上神经母细胞瘤模型，在体外重现NB复杂的血管系统，包括两种类型的血管生成。我们设计了一种基于I型胶原蛋白/纤维蛋白的水凝胶，其紧密模拟NB的生理组成和肿瘤硬度。这种生物材料为NB和内皮细胞的存活创造了一个支持性环境。在微流控芯片内施加与在动脉和毛细血管中观察到的范围一致的生理剪切应力值，促进了血管样结构的成功形成，并触发了NB细胞向TECs的转分化。此处介绍的芯片上血管化神经母细胞瘤模型为基于动物的研究提供了一种有前景的补充策略，具有深入研究NB肿瘤生物学和血管靶向治疗的巨大潜力。
在线版本包含可在10.1007/s44164-023-00064-x获取的补充材料。
