A 3D Bioprinted Human Neurovascular Unit Model of Glioblastoma Tumor Growth

Abstract A 3D bioprinted neurovascular unit (NVU) model was developed to study glioblastoma (GBM) tumor growth in a brain‐like microenvironment. The NVU model included human primary astrocytes, pericytes and brain microvascular endothelial cells, and patient‐derived glioblastoma cells (JHH‐520) were used for this study. We used fluorescence reporters with confocal high content imaging to quantitate real‐time microvascular network formation and tumor growth. Extensive validation of the NVU‐GBM model included immunostaining for brain relevant cellular markers and extracellular matrix components; single cell RNA sequencing to establish physiologically relevant transcriptomics changes; and secretion of NVU and GBM‐relevant cytokines. The scRNAseq revealed changes in gene expression and cytokines secretion associated with wound healing/angiogenesis, including the appearance of an endothelial mesenchymal transition (EndMT) cell population. The NVU‐GBM model was used to test 18 chemotherapeutics and anti‐cancer drugs to assess the pharmacological relevance of the model and robustness for high throughput screening. This article is protected by copyright. All rights reserved