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Updated: Apr 30, 2026
Intranasal Delivery of Therapeutic Stem Cells to Glioblastoma in a Mouse Model
Published on: June 4, 2017
Systemic anticancer neural stem cells in combination with a cardiac glycoside for glioblastoma therapy
Jian Teng1, Seyedali Hejazi, Christian E Badr
1Experimental Therapeutics and Molecular Imaging Laboratory, Neuroscience Center, Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA; Program in Neuroscience, Harvard Medical School, Boston, Massachusetts, USA.
Abstract:
The tumor-tropic properties of neural stem cells (NSCs) have been shown to serve as a novel strategy to deliver therapeutic genes to tumors. Recently, we have reported that the cardiac glycoside lanatoside C (Lan C) sensitizes glioma cells to the anticancer agent tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Here, we engineered an FDA-approved human NSC line to synthesize and secrete TRAIL and the Gaussia luciferase (Gluc) blood reporter. We showed that upon systemic injection, these cells selectively migrate toward tumors in the mice brain across the blood-brain barrier, target invasive glioma stem-like cells, and induce tumor regression when combined with Lan C. Gluc blood assay revealed that 30% of NSCs survived 1 day postsystemic injection and around 0.5% of these cells remained viable after 5 weeks in glioma-bearing mice. This study demonstrates the potential of systemic injection of NSCs to deliver anticancer agents, such as TRAIL, which yields glioma regression when combined with Lan C.
Insights
Engineered neural stem cells (NSCs) deliver tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) across the blood-brain barrier to treat gliomas. Combining TRAIL-secreting NSCs with lanatoside C significantly regressed tumors in mice.
Area of Science:
- Neuroscience
- Oncology
- Biotechnology
Background:
- Neural stem cells (NSCs) possess inherent tumor-tropic properties, making them promising vectors for targeted cancer therapy.
- Lanatoside C (Lan C) enhances glioma cell sensitivity to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a potent anticancer agent.
Purpose of the Study:
- To engineer human NSCs for secreting TRAIL and Gaussia luciferase (Gluc) for glioma treatment.
- To evaluate the efficacy of systemically administered engineered NSCs in targeting and regressing brain tumors, particularly in combination with Lan C.
Main Methods:
- Engineered an FDA-approved human NSC line to express TRAIL and Gluc.
- Administered engineered NSCs systemically to mice with brain gliomas.
- Assessed NSC migration across the blood-brain barrier, tumor targeting, and tumor regression.
- Quantified NSC survival using Gluc blood assays.
Main Results:
- Engineered NSCs selectively migrated to brain tumors across the blood-brain barrier and targeted invasive glioma stem-like cells.
- Combination therapy with TRAIL-secreting NSCs and Lan C induced significant glioma regression in mice.
- NSC survival rates were 30% at 1 day and approximately 0.5% at 5 weeks post-injection in tumor-bearing mice.
Conclusions:
- Systemic injection of engineered NSCs is a viable strategy for delivering therapeutic agents like TRAIL to brain tumors.
- The combination of TRAIL-delivered by NSCs and Lan C shows significant potential for glioma regression.
- This approach offers a novel therapeutic avenue for treating challenging brain cancers.
