Intra-Cavity Stem Cells Target Post-Surgical Brain Tumor Progression In Novel Resection And Recurrence Mouse Models

Surgical resection is a universal component of therapy against aggressive brain tumors. These cancers include glioblastoma (GBM) and medulloblastoma (MB), which are prevalent in older adults and children, respectively. Due to limited pre-clinical models, little is known about the post-operative microenvironment and how it impacts efficacy of local therapies. Cytotoxic stem cells (SCs) have emerged as a promising approach to target these aggressive post-surgical brain cancers, due in large part to their inherent tumor-homing properties. Our goal is to develop scaffold technology to improve stem cell therapy for post-surgical brain tumors. Though, in order to develop this new stem cell technology, there needs to be animal models in which to test this therapy. Thus, in chapter two, we created the first GBM resection and recurrence model in an immune-competent mice. This model allowed us to observe surgery-mediated events that may potentiate tumor aggressiveness and efficacy of local stem therapies. In chapter three, we tested different scaffold materials that were loaded with cytotoxic stem cells in our GBM resection models. We found that therapeutic stem cells loaded on these materials inhibited post-surgical tumor recurrence. Lastly, in chapter four, we utilize stem cell-scaffold technology in an entirely new model of surgical resection, new disease, and new stem cells for pediatric patients. Using therapeutic stem cells derived from pediatric human patients, this therapy delayed post-surgical tumor recurrence and extended median survival in tumor-bearing mice. These studies demonstrate a novel model of GBM and MB resection and recurrence that provided a platform to develop and advance stem cell technologies in a post-surgical cavity. In addition, the results also suggest that intra-cavity SC therapy is a viable new option to effectively control post-operative tumor growth in GBM and MB patients.Doctor of Philosoph