A Bioprinted Volumetric Model of Vascularized Glioblastoma

血管化胶质母细胞瘤的生物打印体积模型

• 批准号: 10717766
• 负责人: ALFREDO QUINONES-HINOJOSA
• 金额: $ 44.64万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-14 至 2028-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10717766
• 关键词: 3-Dimensional; Actins; Affect; Architecture; Astrocytes; Behavior; Biocompatible Materials; Biological; Biology; Blood - brain barrier anatomy; Blood Vessels; Brain; Brain Neoplasms; Cell Communication; Cell Line; Cell Therapy; Cells; Characteristics; Communication; Complex; Coupled; Data; Disease; Drug Screening; Endothelial Cells; Engineering; Environment; Extracellular Matrix; FDA approved; Focal Adhesions; Future; Glioblastoma; Growth; Human; Immune; In Vitro; Light; Macrophage; Malignant Neoplasms; Malignant neoplasm of brain; Methodology; Modeling; Molecular; Mus; Neurons; Operative Surgical Procedures; Outcome; Patients; Pericytes; Pharmaceutical Preparations; Physiological; Proliferating; Property; Quinones; Reaction; Rest; Role; Scheme; Signal Transduction; System; Technology; Testing; Therapeutic Agents; Tissue Model; Tissues; Vascularization; Verteporfin; bioink; bioprinting; blood-brain barrier crossing; cell motility; cell type; chemoradiation; design; digital; experience; improved; in vitro Model; in vivo; in vivo Model; inhibitor; interest; migration; next generation; novel therapeutics; screening; standard of care; tool; translational potential; treatment response; tumor; tumor microenvironment; tumor progression

Abstract The dynamic tumor microenvironment (TME) where cells continuously communicate, migrate, and react to each other and the signals that are secreted, is critical for inducing tumor progression and aggressiveness of most forms of cancer. We have special interest in glioblastoma (GBM) that displays a dynamic and complex TME for which we have developed the necessary tools to dissect it, understand it, and have a positive impact on its treatment. As such, it is necessary to understand the underlying biology in a dynamic and relevant environment. With various degrees of limitation pertaining to currently available in vitro and in vivo models, in this proposal, we aim to leverage our expertise to optimize a unique three-dimensional (3D) human mini-GBM model through the utilization of a light-based bioprinting technology and taking advantage of primary neuronal, vascular, and GBM cells, to more precisely replicate the brain TME in human patients. It is anticipated that, construction of an in vitro 3D human mini-GBM model mimicking not only the cellular compositions but also the extracellular matrix (ECM) properties and importantly, tissue architecture of its in vivo counterpart, will allow us to precisely assess proliferation, migration, and transformation of GBM cells, similar to those already proven in ex vivo GBM organotypic cultures but at much higher availability and throughput for potential drug screening in the future.

摘要 动态肿瘤微环境（TME），细胞在其中不断交流，迁移和反应， 相互作用和分泌的信号，对于诱导肿瘤进展和侵袭性是至关重要的。 大多数形式的癌症。我们对胶质母细胞瘤（GBM）特别感兴趣，GBM显示出动态和复杂的 我们已经开发了必要的工具来剖析它，理解它，并产生积极的影响 关于它的治疗。因此，有必要以动态和相关的方式了解潜在的生物学 环境由于与目前可用的体外和体内模型有关的各种程度的限制， 我们的目标是利用我们的专业知识来优化一个独特的三维（3D）人体迷你GBM 模型通过利用基于光的生物打印技术并利用初级神经元， 血管和GBM细胞，以更精确地复制人类患者的脑TME。预计， 构建体外3D人迷你GBM模型，不仅模拟细胞组成，而且模拟细胞的组成。 细胞外基质（ECM）的性质，重要的是，其在体内对应的组织结构，将允许我们 为了精确评估GBM细胞的增殖、迁移和转化，类似于已经在 离体GBM器官型培养物，但对于潜在的药物筛选具有高得多的可用性和通量， 未来