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This dual mechanism allows GBM cells to successfully organoids also improve drug screening and therapeutic
avoid NK cell cytotoxicity, thereby increasing their survival modeling by providing a more realistic microenvironment,
and invasiveness. These immune evasion mechanisms with GSCs showing differential sensitivity to chemotherapy
present potential targets for the immunotherapy of GBM. and radiation compared to 2D cultures. In addition, the
vascular network helps maintain tumor heterogeneity by
4.1.4. Glioma-associated stromal cells preserving key genetic features and signaling pathways often
Glioma-associated stromal cells (GASCs) exhibit lost in 2D models. However, constructing vascularized GBM
characteristics similar to MSCs and cancer-associated models presents challenges, such as the need for advanced
fibroblasts. They contribute to tumor angiogenesis, invasion, bioengineering to create perfusable vasculature with BBB
and growth by secreting soluble factors and extracellular characteristics.
vesicles. As an integral component of the TME, GASCs
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are increasingly being considered as potential new targets 4.2.1.1. PDX model
for glioma therapy. Patient-derived xenograft (PDX) models have
Lately, researchers have proposed an “ecological trap” demonstrated great research value in the in vivo study of
strategy that leverages the characteristics of GASCs, gliomas. By transplanting patients’ primary tumor tissues
which aims to capture residual brain cancer cells around directly into immunodeficient mice, these models can
the surgical cavity after surgery using biomaterials, largely preserve the original tumor’s tissue architecture,
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creating an artificial niche that concentrates these residual cellular composition, and molecular characteristics. PDX
cells in a specific area for targeted therapy or radiation models not only accurately replicate the microenvironment
therapy. 101,102 This method holds promise in reducing the of human gliomas but also reflect the heterogeneity of
risk of recurrence after surgery, especially when complete tumors, which is one of their key advantages in glioma
tumor resection is challenging. Utilizing biomaterials with research. This allows researchers to study tumor biology
radio-sensitizing and chemotherapeutic properties, such as in detail within an in vivo environment, particularly
bacterial cellulose scaffolds, can further enhance the killing the complex interactions between tumor cells and their
effect on residual tumor cells. These materials can increase microenvironment. In addition, PDX models can be used
the sensitivity of tumors to radiation and chemotherapy to assess responses to various drugs, providing a reliable
drugs, thereby enhancing therapeutic effects and effectively platform for the development of personalized treatment
reducing the likelihood of recurrence. This novel strategy, strategies. Through this model, researchers can better
which combines physical capture, targeted therapy, and understand the biological characteristics of gliomas, screen
biomaterials, not only improves treatment efficiency but the most promising treatment plans, and thus provide a
also significantly reduces post-operative recurrence rates, scientific basis for clinical therapy.
offering new insights into glioma treatment. While PDX models offer advantages in glioma research,
they also face certain limitations. For instance, because
4.2. Construction strategies of organoids in GBM immunodeficient mice lack a fully functional immune
4.2.1. Traditional models and organoids in GBM system, PDX models cannot fully reflect the interactions
research between human tumors and the immune system. 107,108
Consequently, PDX models may not provide complete
Traditional GSC-derived xenograft models face significant references when exploring immunotherapies. In addition,
limitations due to interspecies differences, variability in tumor the tumor growth conditions in mice may differ from those
latency, lack of real-time imaging and genetic manipulation in humans, leading to differences in drug responses.
capabilities, and ethical issues. These challenges restrict
the interpretability of research results and the feasibility of 4.2.2. Construction strategies for organoid models in
clinical translation. 103,104 Similarly, two-dimensional (2D) GBM
monolayer cultures, while convenient for basic research, lack
the complexity of the human extracellular matrix (ECM) and 4.2.2.1. Matrix gel chimeric models
cannot accurately simulate the spatial arrangement of cells Researchers such as Hubert et al. have established
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in the human brain or their interactions with surrounding glioblastoma organoids (GBOs) by embedding single-cell
tissues. This difference means that 2D cultures significantly samples from GBM patients in Matrigel (Figure 1). While
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differ from the actual tumor biological environment and this model simulates the complexity of GBM to some
cannot fully reproduce the complexity of human gliomas. In extent, the lack of a vascular system leads to significant
contrast, vascularized BOs support rapid tumor growth and nutrient gradient changes from the outer regions to the
invasion, accurately mimicking GBM’s aggressive nature. core. Consequently, GSCs are denser and proliferate
Patient-derived GSCs form invasive tumors with microtubes more rapidly in the outer regions, while cells in the inner
that facilitate invasion, similar to human GBMs. Vascularized regions are sparse and grow slowly. This uneven nutrient
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Volume 1 Issue 1 (2025) 8 doi: 10.36922/or.8261