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

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.

SUBMITTER: Bomba HN

PROVIDER: S-EPMC9115686 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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

Bomba Hunter N HN Carey-Ewend Abigail A Sheets Kevin T KT Valdivia Alain A Goetz Morgan M Findlay Ingrid A IA Mercer-Smith Alison A Kass Lauren E LE Khagi Simon S Hingtgen Shawn D SD

Bioengineering & translational medicine 20220121 2

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 ...[more]

PMID: 35600639

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Project description:BackgroundEpistaxis is the most common symptom of hereditary hemorrhagic telangiectasia (HHT), affecting more than 98% of adults with HHT, with significant impact on quality of life. Floseal® has been shown to be effective for the management of anterior epistaxis, but has yet to be thoroughly evaluated in this population. Our goal was to evaluate the efficacy of Floseal® for managing acute anterior epistaxis in patients with HHT.MethodsA pilot prospective clinical trial was conducted at two tertiary referral centres, St. Michael's Hospital, Toronto, Canada and The Ottawa Hospital, Ottawa, Canada. All patients with HHT presenting with acute anterior epistaxis to the two study centres, who enrolled in the study, received Floseal® treatment. The primary outcome measures were achievement of hemostasis and changes in the Epistaxis Severity Score (ESS) between baseline and one-month follow up. Secondary outcome measure included clinical assessment of the nasal cavity.ResultsSeven patients were included in the final analysis. All patients underwent treatment of anterior epistaxis with Floseal® and achieved control of epistaxis within 15-min post-application. Application of Floseal® was well tolerated, with patients reporting a pain score of 3 ± 3.13 out of 10. There was no statistically significant difference noted in ESS scores pre-treatment and one-month follow up, 6.27 ± 2.42 vs. 4.50 ± 2.44, p = 0.179. There was a significant improvement clinically on exam of the nasal cavity between baseline and at one-month follow up, indicated by a decrease in the clinical assessment score, 17.29 ± 7.70 vs. 9.57 ± 7.81 (p = 0.0088).ConclusionsPatients with HHT presenting with acute epistaxis were able to achieve hemostasis with one application of Floseal®, with the procedure being very well tolerated with minimal pain. Although there was no significant change in ESS scores, clinical assessment of the nasal cavity revealed significant improvement at one-month follow up post treatment with Floseal®.Trial registrationThis multi-centered prospective clinical trial was registered with ClinicalTrials.gov ( NCT02638012 ). Registered on December 22, 2015.

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

Publications

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

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