| 1. |
- Bexell, Daniel, et al.
(författare)
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Rat Multipotent Mesenchymal Stromal Cells Lack Long-Distance Tropism to 3 Different Rat Glioma Models
- 2012
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Ingår i: Neurosurgery. - 0148-396X. ; 70:3, s. 731-739
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Viral gene therapy of malignant brain tumors has been restricted by the limited vector distribution within the tumors. Multipotent mesenchymal stromal cells (MSCs) and other precursor cells have shown tropism for gliomas, and these cells are currently being explored as potential vehicles for gene delivery in glioma gene therapy. OBJECTIVE: To investigate MSC migration in detail after intratumoral and extratumoral implantation through syngeneic and orthotopic glioma models. METHODS: Adult rat bone marrow-derived MSCs were transduced to express enhanced green fluorescent protein and implanted either directly into or at a distance from rat gliomas. RESULTS: We found no evidence of long-distance MSC migration through the intact striatum toward syngeneic D74(RG2), N32, and N29 gliomas in the ipsilateral hemisphere or across the corpus callosum to gliomas located in the contralateral hemisphere. After intratumoral injection, MSCs migrated extensively, specifically within N32 gliomas. The MSCs did not proliferate within tumors, suggesting a low risk of malignant transformation of in vivo grafted cell vectors. Using a model for surgical glioma resection, we found that intratumorally grafted MSCs migrate efficiently within glioma remnants after partial surgical resection. CONCLUSION: The findings point to limitations for the use of MSCs as vectors in glioma gene therapy, although intratumoral MSC implantation provides a dense and tumor-specific vector distribution.
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| 2. |
- Bexell, Daniel, et al.
(författare)
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Stem cell-based therapy for malignant glioma.
- 2013
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Ingår i: Cancer Treatment Reviews. - : Elsevier BV. - 1532-1967 .- 0305-7372. ; 39:4, s. 358-365
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Forskningsöversikt (refereegranskat)abstract
- Stem cells have been extensively investigated as tumour-tropic vectors for gene delivery to solid tumours. In this review, we discuss the potential for using stem cells as cellular vector systems in gene therapy for malignant gliomas, with a focus on neural stem cells, and multipotent mesenchymal stromal cells. Tumour cell-derived substances and factors associated with tumour-induced inflammation and tumour neovascularisation can specifically attract stem cells to invasive gliomas. Injected stem cells engineered to produce anti-tumour substances have shown strong therapeutic effects in experimental glioma models. However, the potential caveats include the immunosuppressive functions of multipotent mesenchymal stromal cells, the contribution of stem cells to the pro-tumourigenic stroma, and the malignant transformation of implanted stem cells. In addition, it is not yet known which stem cell types and therapeutic genes will be most effective for the treatment of glioma patients. Here, we highlight the possibilities and problems for translating promising experimental findings in glioma models into the clinic.
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| 3. |
- Gunnarsson, Salina, et al.
(författare)
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Intratumoral IL-7 delivery by mesenchymal stromal cells potentiates IFNgamma-transduced tumor cell immunotherapy of experimental glioma.
- 2010
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Ingår i: Journal of Neuroimmunology. - : Elsevier BV. - 1872-8421 .- 0165-5728. ; 218:1-2, s. 140-144
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Tidskriftsartikel (refereegranskat)abstract
- The present study reports regression of pre-established experimental rat gliomas as a result of combining peripheral immunization using interferon gamma (IFNgamma) transduced autologous tumor cells with local intratumoral delivery of interleukin 7 (IL-7) by mesenchymal stromal cells. IL-7 alone significantly decreased the tumor area and this effect was enhanced with IFNgamma immunization. A higher density of intratumoral T-cells was observed in animals receiving combined therapies compared to rats receiving either cytokine alone suggesting that the therapeutic effect is dependent on a T-cell response.
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| 4. |
- Ströjby, Salina, et al.
(författare)
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Intratumorally implanted mesenchymal stromal cells potentiate peripheral immunotherapy against malignant rat gliomas.
- 2014
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Ingår i: Journal of Neuroimmunology. - : Elsevier BV. - 1872-8421 .- 0165-5728. ; 274:1-2, s. 240-243
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Tidskriftsartikel (refereegranskat)abstract
- Bone marrow-derived mesenchymal stromal cells (MSCs) target glioma extensions and micro-satellites efficiently when implanted intratumorally. Here, we report that intratumoral implantation of MSCs and peripheral immunotherapy with interferon-gamma (IFNγ) producing tumor cells improve the survival of glioma-bearing rats (54% cure rate) compared to MSC alone (0% cure rate) or immunotherapy alone (21% cure rate) by enforcing an intratumoral CD8(+) T cell response. Further analysis revealed that the MSCs up-regulate MHC classes I and II in response to IFNγ treatment in vitro and secrete low amounts of immunosuppressive molecules prostaglandin E2 and interleukin-10.
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