title: Monitoring the Bystander Killing Effect of Human Multipotent Stem Cells for Treatment of Malignant Brain Tumors.
abstract: Tumor infiltrating stem cells have been suggested as a vehicle for the delivery of a suicide gene towards otherwise difficult to treat tumors like glioma. We have used herpes simplex virus thymidine kinase expressing human multipotent adult progenitor cells in two brain tumor models (hU87 and Hs683) in immune-compromised mice. In order to determine the best time point for the administration of the codrug ganciclovir, the stem cell distribution and viability were monitored in vivo using bioluminescence (BLI) and magnetic resonance imaging (MRI). Treatment was assessed by in vivo BLI and MRI of the tumors. We were able to show that suicide gene therapy using HSV-tk expressing stem cells can be followed in vivo by MRI and BLI. This has the advantage that (1) outliers can be detected earlier, (2) GCV treatment can be initiated based on stem cell distribution rather than on empirical time points, and (3) a more thorough follow-up can be provided prior to and after treatment of these animals. In contrast to rodent stem cell and tumor models, treatment success was limited in our model using human cell lines. This was most likely due to the lack of immune components in the immune-compromised rodents.
authors.affiliation: Biomedical MRI, Department of Imaging and Pathology, KU Leuven, 3000 Leuven, Belgium; Molecular Small Animal Imaging Center, KU Leuven, 3000 Leuven, Belgium.
authors.forename: Cindy
authors.initials: C
authors.lastname: Leten
authors.affiliation: Biomedical MRI, Department of Imaging and Pathology, KU Leuven, 3000 Leuven, Belgium; Imec, 3000 Leuven, Belgium.
authors.forename: Jesse
authors.initials: J
authors.lastname: Trekker
authors.affiliation: Biomedical MRI, Department of Imaging and Pathology, KU Leuven, 3000 Leuven, Belgium; Morphology Research Group, Biomedical Research Institute, Hasselt University, 3590 Diepenbeek, Belgium.
authors.forename: Tom
authors.initials: T
authors.lastname: Struys
authors.affiliation: Department of Development and Regeneration, Stem Cell Institute, KU Leuven, 3000 Leuven, Belgium.
authors.forename: Valerie D
authors.initials: VD
authors.lastname: Roobrouck
authors.affiliation: Biomedical MRI, Department of Imaging and Pathology, KU Leuven, 3000 Leuven, Belgium; Molecular Small Animal Imaging Center, KU Leuven, 3000 Leuven, Belgium; Division of Radiology, University Hospitals Leuven, 3000 Leuven, Belgium.
authors.forename: Tom
authors.initials: T
authors.lastname: Dresselaers
authors.affiliation: Biomedical MRI, Department of Imaging and Pathology, KU Leuven, 3000 Leuven, Belgium; Molecular Small Animal Imaging Center, KU Leuven, 3000 Leuven, Belgium.
authors.forename: Greetje
authors.initials: G
authors.lastname: Vande Velde
authors.affiliation: Morphology Research Group, Biomedical Research Institute, Hasselt University, 3590 Diepenbeek, Belgium.
authors.forename: Ivo
authors.initials: I
authors.lastname: Lambrichts
authors.affiliation: Department of Development and Regeneration, Stem Cell Institute, KU Leuven, 3000 Leuven, Belgium.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Verfaillie
authors.affiliation: Biomedical MRI, Department of Imaging and Pathology, KU Leuven, 3000 Leuven, Belgium; Molecular Small Animal Imaging Center, KU Leuven, 3000 Leuven, Belgium.
authors.forename: Uwe
authors.initials: U
authors.lastname: Himmelreich