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Updated: Nov 30, 2025
A 3D Spheroid Model for Glioblastoma
Published on: April 9, 2020
Engineering Three-Dimensional Tumor Models to Study Glioma Cancer Stem Cells and Tumor Microenvironment
Henry Ruiz-Garcia1,2, Keila Alvarado-Estrada2, Paula Schiapparelli2
1Department of Radiation Oncology, Mayo Clinic, Jacksonville, FL, United States.
Abstract:
Glioblastoma (GBM) is the most common and devastating primary brain tumor, leading to a uniform fatality after diagnosis. A major difficulty in eradicating GBM is the presence of microscopic residual infiltrating disease remaining after multimodality treatment. Glioma cancer stem cells (CSCs) have been pinpointed as the treatment-resistant tumor component that seeds ultimate tumor progression. Despite the key role of CSCs, the ideal preclinical model to study the genetic and epigenetic landmarks driving their malignant behavior while simulating an accurate interaction with the tumor microenvironment (TME) is still missing. The introduction of three-dimensional (3D) tumor platforms, such as organoids and 3D bioprinting, has allowed for a better representation of the pathophysiologic interactions between glioma CSCs and the TME. Thus, these technologies have enabled a more detailed study of glioma biology, tumor angiogenesis, treatment resistance, and even performing high-throughput screening assays of drug susceptibility. First, we will review the foundation of glioma biology and biomechanics of the TME, and then the most up-to-date insights about the applicability of these new tools in malignant glioma research.
Insights
Three-dimensional (3D) tumor models like organoids and bioprinting offer better insights into glioblastoma (GBM) biology and treatment resistance by simulating cancer stem cells (CSCs) and the tumor microenvironment (TME). These advanced preclinical tools are crucial for understanding GBM progression and developing new therapies.
Area of Science:
- Neuro-oncology
- Biotechnology
- Cancer Biology
Background:
- Glioblastoma (GBM) is an aggressive brain tumor with poor prognosis.
- Microscopic residual disease and treatment resistance, driven by glioma cancer stem cells (CSCs), hinder effective eradication.
- Current preclinical models lack accurate representation of CSCs within the tumor microenvironment (TME).
Purpose of the Study:
- To review the foundational aspects of glioma biology and TME biomechanics.
- To explore the application of advanced 3D tumor platforms in malignant glioma research.
- To highlight how organoids and 3D bioprinting advance the study of GBM.
Main Methods:
- Review of existing literature on glioma biology, TME, and 3D tumor models.
- Analysis of the utility of organoids and 3D bioprinting in simulating glioma pathophysiology.
- Discussion of applications in studying tumor angiogenesis, treatment resistance, and drug screening.
Main Results:
- 3D tumor platforms provide a more accurate model for studying glioma CSCs and TME interactions.
- These models facilitate a deeper understanding of GBM biology, angiogenesis, and resistance mechanisms.
- Organoids and bioprinting enable high-throughput drug screening for GBM therapeutics.
Conclusions:
- Advanced 3D tumor models are essential for overcoming limitations in current GBM research.
- These technologies offer promising avenues for investigating GBM pathogenesis and developing novel treatment strategies.
- The integration of 3D platforms is pivotal for future advancements in treating malignant gliomas.
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