Glioblastoma Organoid Technology: Approach to Target the Complex Tumor Microenvironment with Promising Drug...

Area of Science:

• Neuro-oncology
• 3D cell culture technology
• Biomedical engineering

Background:

• Glioblastoma (GBM) is a lethal brain tumor with poor prognosis due to its complex tumor microenvironment (TME) and drug resistance.
• Three-dimensional (3D) organoid technology offers a physiologically relevant in vitro model for GBM, mimicking tumor architecture and heterogeneity.
• Current GBM organoid models lack crucial components like immune cells and vasculature, limiting their translational potential, especially for immunotherapy.

Purpose of the Study:

• To address limitations in current glioblastoma (GBM) organoid models.
• To propose engineered cell-based strategies and Adult Stem Cell (AdSC)-derived organoids for enhanced GBM modeling.
• To improve the accuracy and clinical relevance of in vitro GBM research.

Main Methods:

• Advocating for engineered cell-based strategies and Adult Stem Cell (AdSC)-derived organoids.
• Enhancing organoid cell properties and integrating endothelial and immune components.
• Developing a next-generation platform for glioblastoma research.

Main Results:

• Current GBM organoid models fail to fully recapitulate the in vivo TME, impacting drug screening and personalized therapy.
• Existing models like Neo-Cor and GLICO have limitations in reflecting patient heterogeneity or require extensive preparation.
• Patient-derived organoids may suffer from genetic drift during prolonged culture.

Conclusions:

• Engineered AdSC-derived organoids offer a superior platform for modeling glioblastoma.
• This approach enhances accuracy in predicting drug responsiveness and facilitates chemosensitization studies.
• The proposed improvements bring organoid technology closer to clinical translation for glioblastoma research.