Stereotactic intracranial implantation of patient-derived glioblastoma cells in rats: A xenograft modeling approach.

Abstract

BACKGROUND: Glioblastoma (GBM) is an aggressive primary brain cancer with a poor prognosis. Preclinical animal models are essential for studying GBM pathophysiology and therapy; however, existing models often fail to fully capture the tumor's heterogeneity and the partially immunodeficient microenvironment critical to its progression. NEW METHOD: We developed a novel GBM model using the stereotactic implantation of primary patient-derived GBM cells from various donors into the brains of rats subjected to transient, partial immune suppression. RESULTS: This model combines the biological heterogeneity of patient-derived cells with the anatomical advantages of a larger rodent brain, improving spatial tumor localization. The use of a mixed primary cell population better recapitulates human GBM heterogeneity. Furthermore, the model's partially preserved immune environment allows for the investigation of tumor-immune interactions. COMPARISON WITH EXISTING METHODS: Unlike fully immunodeficient models, our approach maintains a more physiologically relevant, partially intact immune system. Compared to murine models, the rat brain offers superior spatial resolution for tumor analysis and intervention. CONCLUSIONS: This method provides a reliable and translational platform that enhances the fidelity of preclinical GBM research. It offers an improved tool for drug evaluation and the development of personalized therapeutic strategies by more accurately mimicking the complex and heterogeneous nature of human GBM.