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

• Published in: Advanced healthcare materials Vol. 13; no. 15; pp. e2302831 - n/a
• Main Authors: Tung, Yen‐Ting, Chen, Yu‐Chi, Derr, Kristy, Wilson, Kelli, Song, Min Jae, Ferrer, Marc
• Format: Journal Article
• Language: English
• Published: Germany 01.06.2024
• Subjects: 3D Bioprinting; Astrocytes - metabolism; Astrocytes - pathology; Bioprinting - methods; Brain Neoplasms - metabolism; Brain Neoplasms - pathology; Cell Line, Tumor; Endothelial Cells - metabolism; Endothelial Cells - pathology; Glioblastoma - metabolism; Glioblastoma - pathology; glioblastomas; high‐throughput screening; Humans; Neovascularization, Pathologic - metabolism; Neovascularization, Pathologic - pathology; neurovascular unit; Pericytes - metabolism; Pericytes - pathology; Printing, Three-Dimensional; transcriptomics; Tumor Microenvironment; 3D Bioprinting; transcriptomics; glioblastomas; high‐throughput screening; neurovascular unit
• ISSN: 2192-2640; 2192-2659
• DOI: 10.1002/adhm.202302831

A 3D bioprinted neurovascular unit (NVU) model is developed to study glioblastoma (GBM) tumor growth in a brain‐like microenvironment. The NVU model includes human primary astrocytes, pericytes and brain microvascular endothelial cells, and patient‐derived glioblastoma cells (JHH‐520) are used for this study. Fluorescence reporters are used with confocal high content imaging to quantitate real‐time microvascular network formation and tumor growth. Extensive validation of the NVU‐GBM model includes immunostaining for brain relevant cellular markers and extracellular matrix components; single cell RNA sequencing (scRNAseq) to establish physiologically relevant transcriptomics changes; and secretion of NVU and GBM‐relevant cytokines. The scRNAseq reveals changes in gene expression and cytokines secretion associated with wound healing/angiogenesis, including the appearance of an endothelial mesenchymal transition cell population. The NVU‐GBM model is used to test 18 chemotherapeutics and anti‐cancer drugs to assess the pharmacological relevance of the model and robustness for high throughput screening. A high‐throughput amenable 3D bioprinted neurovascular unit (NVU) creates a patient‐derived glioblastoma (GBM) growth assay using human primary brain cells and patient‐derived GBM cells in a 96‐well plate with real‐time readouts of angiogenesis and GBM growth for drug screening. Rigorous validation of the NVU model uses scRNAseq analysis, confocal microscopy, and pharmacological relevance tests for drug discovery and development.