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TRAIL-engineered bone marrow-derived mesenchymal stem cells: TRAIL expression and cytotoxic effects on C6 glioma
Xiang-Jun Tang1, Jun-Ti Lu, Han-Jun Tu
1University of British Columbia, 400-828 West 10th Avenue, Vancouver, BC, V5Z 1L8 Canada. Tel: +1 6048754111 ext. 62501, ljdai@mail.ubc.ca or longjundai@gmail.com.
Background:
TNF-related apoptosis-inducing ligand (TRAIL) is considered as a tumor cell-specific cytotoxic agent. Through the aid of mesenchymal stem cells (MSCs), TRAIL is capable of inducing apoptosis of tumor cells in tumor sites. The present study was performed to investigate the cytotoxic effects of TRAIL-engineered MSCs on glioblastoma cells (C6) in vitro.
Materials And Methods:
An expression vector of secreting form of TRAIL was used to engineer MSCs. The cytotoxic effects of TRAIL-transfected MSCs on C6 cells were invstigated using the MTT method and Hochest33258 staining after co-culture of the two cell types.
Results:
TRAIL and control plasmid transfection of MSCs showed no significant effect on MSC's viability (p>0.05). A significant inhibition of C6 cells was observed when they were co-cultured with TRAIL-engineered MSCs (63.7%±0.12, p<0.05).
Conclusion:
Mesenchymal stem cells were very well tolerant to the transfection of TRAIL-bearing vectors. The cytotoxic effects of TRAIL-engineered MSCs on C6 cells indicates the therapeutic potential of this strategy for treatment of glioblastoma patients.
Insights
Engineered mesenchymal stem cells (MSCs) expressing TNF-related apoptosis-inducing ligand (TRAIL) effectively killed glioblastoma cells in vitro. This TRAIL-MSC therapy shows promise for treating glioblastoma.
Area of Science:
- Biotechnology
- Cancer Biology
- Cell Therapy
Background:
- TNF-related apoptosis-inducing ligand (TRAIL) exhibits tumor cell-specific cytotoxicity.
- Mesenchymal stem cells (MSCs) can deliver TRAIL to tumor sites to induce apoptosis.
- Glioblastoma remains a challenging cancer with limited treatment options.
Purpose of the Study:
- To investigate the efficacy of TRAIL-engineered MSCs against glioblastoma (C6) cells in vitro.
- To assess the therapeutic potential of combining MSCs with TRAIL for glioblastoma treatment.
Main Methods:
- MSCs were engineered to express a secreting form of TRAIL using an expression vector.
- The cytotoxic effects of TRAIL-transfected MSCs on C6 cells were evaluated.
- MTT assay and Hochest33258 staining were employed to assess cell viability and apoptosis.
Main Results:
- TRAIL or control plasmid transfection did not significantly affect MSC viability (p>0.05).
- Co-culture with TRAIL-engineered MSCs resulted in significant inhibition of C6 glioblastoma cells (63.7%±0.12, p<0.05).
Conclusions:
- MSCs demonstrated good tolerance to TRAIL-bearing vector transfection.
- TRAIL-engineered MSCs exhibit significant cytotoxic effects on glioblastoma cells.
- This strategy holds therapeutic potential for glioblastoma treatment.
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