Kim Jisoo, Jang Jinah, Cho Dong-Woo
School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang, South Korea.
Department of Mechanical Engineering, Pohang University of Science and Technology, Pohang, South Korea.
Front Bioeng Biotechnol. 2021 Mar 17;9:605819. doi: 10.3389/fbioe.2021.605819. eCollection 2021.
A physiologically relevant tumor microenvironment is favorable for the progression and growth of gastric cancer cells. To simulate the tumor-specific conditions of environments, several biomaterials engineering studies have investigated three-dimensional (3D) cultures. However, the implementation of such cultures remains limited because of challenges in outlining the biochemical and biophysical characteristics of the gastric cancer microenvironment. In this study, we developed a 3D cell printing-based gastric cancer model, using a combination of gastric tissue-specific bioinks and cellulose nanoparticles (CN) to provide adequate stiffness to gastric cancer cells. To create a 3D gastric tissue-specific microenvironment, we developed a decellularization process for a gastric tissue-derived decellularized extracellular matrix (g-dECM) bioink, and investigated the effect of the g-dECM bioink on promoting the aggressiveness of gastric cancer cells using histological and genetic validation methods. We found that incorporating CN in the matrix improves its mechanical properties, which supports the progression of gastric cancer. These mechanical properties are distinguishing characteristics that can facilitate the development of an gastric cancer model. Further, the CN-supplemented g-dECM bioink was used to print a variety of free-standing 3D shapes, including gastric rugae. These results indicate that the proposed model can be used to develop a physiologically relevant gastric cancer system that can be used in future preclinical trials.
生理相关的肿瘤微环境有利于胃癌细胞的进展和生长。为了模拟肿瘤特异性的环境条件，一些生物材料工程研究对三维（3D）培养进行了研究。然而，由于在勾勒胃癌微环境的生化和生物物理特征方面存在挑战，此类培养的应用仍然有限。在本研究中，我们开发了一种基于3D细胞打印的胃癌模型，使用胃组织特异性生物墨水和纤维素纳米颗粒（CN）的组合为胃癌细胞提供足够的硬度。为了创建3D胃组织特异性微环境，我们开发了一种用于胃组织衍生的脱细胞细胞外基质（g-dECM）生物墨水的脱细胞过程，并使用组织学和基因验证方法研究了g-dECM生物墨水对促进胃癌细胞侵袭性的影响。我们发现，在基质中加入CN可改善其机械性能，这支持了胃癌的进展。这些机械性能是有助于开发胃癌模型的显著特征。此外，添加CN的g-dECM生物墨水被用于打印各种独立的3D形状，包括胃皱襞。这些结果表明，所提出的模型可用于开发一种生理相关的胃癌系统，可用于未来的临床前试验。
