Engineered stem cell (SC)-based therapy holds enormous promise for treating the incurable brain cancer glioblastoma (GBM). Retention of the cytotoxic SCs within the GBM resection is one of the greatest challenges to this approach. Here, we describe a biocompatible polymeric bio-scaffold (bPBS) transplant strategy that is capable of delivering and retaining tumor-homing cytotoxic SCs to prevent recurrence of surgically resected GBM. As a new approach to GBM therapy, we created bPBS bearing

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... eleasing human mesenchymal stem cells (hMSCs). Using unique models of GBM resection/recurrence in mice, we discovered that bPBS-based transplant stabilizes cytotoxic hMSCs in the surgical cavity, increasing SC retention 5-fold and prolonging persistence 3-fold compared to standard direct injection. Time-lapse kinetic imaging and analysis showed the pPBS still allowed hMSCs to rapidly migrate off the matrix as they homed to GBMs but not normal cells of the brain. 3-dimension co-culture assays showed cytotoxic hMSC/bPBS treatment reduced the viability of multiple human GBM cells 50-90%. In vivo, bPBS loaded with cytotoxic hMSCs releasing the anti-tumor protein TRAIL (bPBS sTR ) transplanted over established human GBM xenografts reduced tumor volumes 3-fold. Mimicking clinical GBM patient therapy, lining the post-operative GBM surgical cavity with bPBS sTR implants reduced postsurgical GBM volumes 2.3-fold and prolonged post-surgical median survival from 13.5 to 31 days compared to control-treated mice. These results suggest that polymeric bio-scaffold SC therapies could be an innovative new approach to improve the outcomes of patients suffering from terminal brain cancer.