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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/19678

Title: Assessment of bystander killing-mediated therapy of malignant brain tumors using a multimodal imaging approach
Authors: Leten, Cindy
Trekker, Jesse
Struys, Tom
Dresselaers, Tom
Gijsbers, Rik
Vande Velde, Greetje
Lambrichts, Ivo
Van der Linden, Annemie
Verfaillie, Catherine M.
Himmelreich, Uwe
Issue Date: 2015
Citation: Stem Cell Research & Therapy, 6
Abstract: Introduction: In this study, we planned to assess if adult stem cell-based suicide gene therapy can efficiently eliminate glioblastoma cells in vivo. We investigated the therapeutic potential of mouse Oct4-bone marrow multipotent adult progenitor cells (mOct4(-) BM-MAPCs) in a mouse glioblastoma model, guided by multimodal in vivo imaging methods to identify therapeutic windows. Methods: Magnetic resonance imaging (MRI) of animals, wherein 5 x 10(5) syngeneic enhanced green fluorescent protein-firefly luciferase-herpes simplex virus thymidine kinase (eGFP-fLuc-HSV-TK) expressing and superparamagnetic iron oxide nanoparticle labeled (1 % or 10 %) mOct4(-) BM-MAPCs were grafted in glioblastoma (GL261)-bearing animals, showed that labeled mOct4(-) BM-MAPCs were located in and in close proximity to the tumor. Subsequently, ganciclovir (GCV) treatment was commenced and the fate of both the MAPCs and the tumor were followed by multimodal imaging (MRI and bioluminescence imaging). Results: In the majority of GCV-treated, but not phosphate-buffered saline-treated animals, a significant difference was found in mOct4(-) BM-MAPC viability and tumor size at the end of treatment. Noteworthy, in some phosphate-buffered saline-treated animals (33 %), a significant decrease in tumor size was seen compared to sham-operated animals, which could potentially also be caused by a synergistic effect of the immune-modulatory stem cells. Conclusions: Suicide gene therapy using mOct4(-) BM-MAPCs as cellular carriers was effective in reducing the tumor size in the majority of the GCV-treated animals leading to a longer progression-free survival compared to sham-operated animals. This treatment could be followed and guided noninvasively in vivo by MRI and bioluminescence imaging. Noninvasive imaging is of particular interest for a rapid and efficient validation of stem cell-based therapeutic approaches for glioblastoma and hereby contributes to a better understanding and optimization of a promising therapeutic approach for glioblastoma patients.
Notes: [Leten, Cindy; Trekker, Jesse; Struys, Tom; Dresselaers, Tom; Vande Velde, Greetje; Himmelreich, Uwe] Katholieke Univ Leuven, Dept Imaging & Pathol, Biomed MRI, B-3000 Leuven, Belgium. [Leten, Cindy; Dresselaers, Tom; Vande Velde, Greetje; Himmelreich, Uwe] Katholieke Univ Leuven, Mol Small Anim Imaging Ctr, B-3000 Leuven, Belgium. [Trekker, Jesse] IMEC, Dept Life Sci Technol, B-3001 Leuven, Belgium. [Struys, Tom; Lambrichts, Ivo] Hasselt Univ, Histol Lab, Biomed Res Inst, B-3500 Hasselt, Belgium. [Gijsbers, Rik] Katholieke Univ Leuven, Lab Mol Virol & Gene Therapy, B-3000 Leuven, Belgium. [Gijsbers, Rik] Katholieke Univ Leuven, Leuven Viral Vector Core, B-3000 Leuven, Belgium. [Van der Linden, Annemie] Univ Antwerp, BioImaging Lab, B-2610 Antwerp, Belgium. [Verfaillie, Catherine M.] Katholieke Univ Leuven, Dept Dev & Regenerat, Stem Cell Inst, B-3000 Leuven, Belgium.
URI: http://hdl.handle.net/1942/19678
DOI: 10.1186/s13287-015-0157-3
ISI #: 000360787900002
ISSN: 1757-6512
Category: A1
Type: Journal Contribution
Validation: ecoom, 2016
Appears in Collections: Research publications

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