Brain Tumor Stem Cells: Characterization in an Immunocompetent Brain Tumor Model and Potential Therapeutic Strategies

The prognosis of patients with human high grade gliomas (hHGG) remains grim. Therapeutic challenges include lack of suitable animal models, the recent discovery of brain tumor stem cells (BTSC), and difficulty in delivering therapeutics across the blood-brain barrier. The aims of this study include the characterization of the CT2A brain tumor model in the immunocompetent mouse, direct targeting of BTSC by bone morphogenic protein (BMP4), and assessment of migratory capacity of embryonic stem cell (ESC)-derived astrocytes as potential vehicle for gene delivery in hHGG. Our results show that the CT2A model provides 100% tumorigenesis rate with a BTSC population expressing stem cell (SC) markers and showing proliferation and invasion mimicking hHGG. Direct targeting of BTSC resulted in increased differentiation toward astrocytic lineage. Finally, ESC-derived astrocytes showed migratory and "homing" characteristics of SC. In summary, our data supports the concept that CT2A is a useful pre-clinical model and can be used to identify new therapies to target BTSC. Additionally, our results corroborate previous data suggesting that ESC-derived astrocytes are a promising strategy for cell-based gene therapy.