SC-15 * ISOLATING GLIOBLASTOMA TUMOR INITIATING PROGENITOR CELLS FROM THE SUBVENTRICULAR ZONE USING A NOVEL MINIMALLY INVASIVE APPROACH

Abstract

Over 50% of brain tumor patients do not have effective therapeutic options, partly due to the delicate location of the brain tumor in the brain, suggesting the need for improved neurosurgical approaches. Furthermore, for those patients who do receive standard care, although tumor shrinkage is often observed, 90% of patients with Glioblastoma Multiforme (GBM) exhibit tumor relapse. Mechanistically, this could be attributed to residual GBM tumor initiating cells (GTICs). One important variable in the isolation of GTICs from patients may be the anatomic site from where they are harvested. We report a novel minimally invasive corridor-based approach to resect the primary GBM, but also move beyond the Magnetic Resonance Image (MRI)-visible GBM in a more accurate, efficient, and targeted manner towards the subventricular zone (SVZ). Most importantly, the reported approach preserves the sample biology and integrity while respecting surrounding healthy tissues. Through this approach, we harvested samples from four consented GBM patients from two locations, the MRI-visible GBM and the SVZ. We demonstrate that GTICs can be isolated with a 100% success rate from the SVZ as oppose to 50% from the MRI-visible GBM. SVZ-GTICs were tumorigenic in xenografts and contained GBM-associated mutations EGFR and PTEN confirming that they were not endogenous neural stem cells residing in the SVZ. The high harvest rate of GTICs can be attributed to the closed-loop system that we employed which allowed the harvested samples to be kept in physiologic conditions, preserving sample biology and integrity. Furthermore, it could also be attributed to our ability to isolate GTICs directly from their niche in the SVZ. In conclusion, we demonstrate here the directed and targeted isolation of GTICs from their SVZ niche in human GBM patients intraoperatively.