Use of FLOSEAL® as a scaffold and its impact on induced neural stem cell phenotype, persistence, and efficacy

Bioengineering & Translational Medicine

Simon Khagi¹  Kevin T. Sheets²  Abigail Carey‐Ewend²  Shawn D. Hingtgen²  Lauren E. Kass²  Hunter N. Bomba²  Morgan Goetz²  Ingrid A. Findlay²  Alain Valdivia²  Alison Mercer‐Smith² 

[1] Department of Neurosurgery The University of North Carolina at Chapel Hill Chapel Hill North Carolina USA;Division of Pharmacoengineering and Molecular Pharmaceutics UNC Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill Chapel Hill North Carolina USA;

关键词: fibrin;    gelatin;    glioblastoma;    neural stem cell;    scaffold;    TRAIL;   

DOI  :  10.1002/btm2.10283

来源: DOAJ

【 摘 要 】

Abstract Induced neural stem cells (iNSCs) have emerged as a promising therapeutic platform for glioblastoma (GBM). iNSCs have the innate ability to home to tumor foci, making them ideal carriers for antitumor payloads. However, the in vivo persistence of iNSCs limits their therapeutic potential. We hypothesized that by encapsulating iNSCs in the FDA‐approved, hemostatic matrix FLOSEAL®, we could increase their persistence and, as a result, therapeutic durability. Encapsulated iNSCs persisted for 95 days, whereas iNSCs injected into the brain parenchyma persisted only 2 weeks in mice. Two orthotopic GBM tumor models were used to test the efficacy of encapsulated iNSCs. In the GBM8 tumor model, mice that received therapeutic iNSCs encapsulated in FLOSEAL® survived 30 to 60 days longer than mice that received nonencapsulated cells. However, the U87 tumor model showed no significant differences in survival between these two groups, likely due to the more solid and dense nature of the tumor. Interestingly, the interaction of iNSCs with FLOSEAL® appears to downregulate some markers of proliferation, anti‐apoptosis, migration, and therapy which could also play a role in treatment efficacy and durability. Our results demonstrate that while FLOSEAL® significantly improves iNSC persistence, this alone is insufficient to enhance therapeutic durability.

【 授权许可】

Unknown