A Biomaterials Approach to Increasing the Persistence of Induced Neural Stem Cells in the Glioblastoma Tumor Resection Cavity

Despite medical and technological advances, the survival statistics for patients diagnosed with glioblastoma have remained stagnant for more than three decades. The invasiveness and high recurrence rate of glioblastoma leave both local and systemic therapies ineffective and the median survival at an abysmal 12-15 months post-diagnosis. To combat this deadly disease, researchers have employed induced neural stem cells (iNSCs). Derived from a patient’s fibroblasts, iNSCs have shown the remarkable ability to home to and kill distant tumor foci when engineered with lentiviruses encoding cytotoxic proteins and a stem cell-specific transcription factor. Yet, when injected into the brain parenchyma in a saline suspension, iNSCs are cleared in less than two weeks, thus limiting therapeutic durability. Previous studies have reported that by encapsulating iNSCs in a biomaterial matrix, persistence can be significantly improved. This dissertation explores how increasing the persistence of iNSCs in vivo impacts therapeutic durability and overall survival. Additionally, the safety and toxicity profile of iNSCs, delivered in both a biomaterial matrix and injected intracerebroventricularly, is characterized in a canine model. Lastly, a bio-inspired matrix for reducing cost and increasing throughput of cell therapy studies is presented.Doctor of Philosoph