Related Experiment Video
Updated: Apr 4, 2026
Modeling Brain Metastasis by Internal Carotid Artery Injection of Cancer Cells
Published on: August 2, 2022
Assessment of bystander killing-mediated therapy of malignant brain tumors using a multimodal imaging approach
Cindy Leten1,2, Jesse Trekker3,4, Tom Struys5,6
1Biomedical MRI, Department of Imaging and Pathology, KU Leuven, 3000, Leuven, Belgium. cindy.leten@gmail.com.
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 × 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.
Insights
Adult stem cell suicide gene therapy effectively reduced glioblastoma tumor size in mice. This approach, using mouse Oct4(-) bone marrow multipotent adult progenitor cells (mOct4(-) BM-MAPCs) and ganciclovir, showed promise for glioblastoma treatment.
Area of Science:
- Oncology
- Stem Cell Therapy
- Gene Therapy
Background:
- Glioblastoma multiforme (GBM) is an aggressive brain tumor with limited treatment options.
- Adult stem cells offer potential as targeted delivery vehicles for cancer therapies.
- Suicide gene therapy aims to eliminate cancer cells by introducing genes that induce cell death upon activation.
Purpose of the Study:
- To evaluate the efficacy of adult stem cell-based suicide gene therapy in eliminating glioblastoma cells in vivo.
- To investigate the therapeutic potential of mouse Oct4(-) bone marrow multipotent adult progenitor cells (mOct4(-) BM-MAPCs) in a preclinical glioblastoma model.
- To utilize multimodal in vivo imaging for guiding and monitoring the therapeutic process.
Main Methods:
- Mouse glioblastoma (GL261) model established in syngeneic animals.
- Transplantation of enhanced green fluorescent protein-firefly luciferase-herpes simplex virus thymidine kinase (eGFP-fLuc-HSV-TK) expressing and nanoparticle-labeled mOct4(-) BM-MAPCs.
- Treatment with ganciclovir (GCV) and monitoring via magnetic resonance imaging (MRI) and bioluminescence imaging (BLI).
Main Results:
- GCV treatment significantly reduced tumor size and improved mOct4(-) BM-MAPC viability in most treated animals compared to controls.
- Non-GCV treated animals showed some tumor reduction, potentially due to immune-modulatory effects of stem cells.
- Multimodal imaging successfully tracked stem cell location and tumor response throughout the study.
Conclusions:
- Suicide gene therapy utilizing mOct4(-) BM-MAPCs as cellular carriers is effective in reducing glioblastoma tumor size and improving progression-free survival.
- Noninvasive MRI and BLI are valuable tools for real-time monitoring and validation of stem cell-based therapies for glioblastoma.
- This approach offers a promising strategy for optimizing glioblastoma treatment and improving patient outcomes.
