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

基本信息

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
项目类别：
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

项目摘要

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.

抽象的动态肿瘤微环境（TME），其中细胞连续交流，迁移和反应彼此和分泌的信号对于诱导肿瘤进展和侵略性至关重要大多数形式的癌症。我们对显示动态和复杂的胶质母细胞瘤（GBM）特别感兴趣我们为其开发了必要工具来剖析它，理解并产生积极影响的TME 在治疗中。因此，有必要了解动态和相关的基本生物学环境。与当前可用的体外和体内模型相关的不同程度的限制这项建议，我们旨在利用我们的专业知识来优化独特的三维（3D）人类迷你GBM 通过利用基于光的生物打印技术并利用原发性神经元的模型，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人类迷你GBM模型，不仅模仿细胞组成，还模仿细胞外基质（ECM）特性，重要的是，其体内的组织结构将使我们允许我们精确评估GBM细胞的增殖，迁移和转化，类似于已经证明的离体GBM器官型培养物，但可用性和吞吐量要高得多未来。