A Bioprinted Volumetric Model of Vascularized Glioblastoma

摘要 动态的肿瘤微环境(TME)，细胞在其中持续交流、迁移和反应 彼此之间以及分泌的信号，对于诱导肿瘤的进展和侵袭性至关重要 大多数形式的癌症。我们对胶质母细胞瘤(GBM)特别感兴趣，它表现出动态和复杂的 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，有必要在动态和相关的基础上理解生物学 环境。与目前可用的体外和体内模型有关的不同程度的限制，在 这项提议，我们的目标是利用我们的专业知识来优化一种独特的三维(3D)人体微型GBM 通过利用基于光的生物打印技术和利用初级神经元的优势， 血管和GBM细胞，以更精确地复制人类患者的大脑TME。预计， 一种既能模拟细胞成分，又能模拟人体微小基底膜的体外3D模型的构建 细胞外基质(ECM)的特性，以及重要的是，它在体内的组织结构，将使我们能够 精确评估GBM细胞的增殖、迁移和转化，类似于已在 体外GBM器官型培养，但具有更高的可用性和吞吐量，可用于潜在的药物筛选 未来。

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.