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Co-culture of Glioblastoma Stem-like Cells on Patterned Neurons to Study Migration and Cellular Interactions
Published on: February 24, 2021
Analysis of glioblastoma tumor coverage by oncolytic virus-loaded neural stem cells using MRI-based tracking and
R A Morshed1, M Gutova2, J Juliano3
1The Brain Tumor Center, Pritzker School of Medicine, The University of Chicago, Chicago, IL, USA.
Abstract:
In preclinical studies, neural stem cell (NSC)-based delivery of oncolytic virus has shown great promise in the treatment of malignant glioma. Ensuring the success of this therapy will require critical evaluation of the spatial distribution of virus after NSC transplantation. In this study, the patient-derived GBM43 human glioma line was established in the brain of athymic nude mice, followed by the administration of NSCs loaded with conditionally replicating oncolytic adenovirus (NSC-CRAd-S-pk7). We determined the tumor coverage potential of oncolytic adenovirus by examining NSC distribution using magnetic resonance (MR) imaging and by three-dimensional reconstruction from ex vivo tissue specimens. We demonstrate that unmodified NSCs and NSC-CRAd-S-pk7 exhibit a similar distribution pattern with most prominent localization occurring at the tumor margins. We were further able to visualize the accumulation of these cells at tumor sites via T2-weighted MR imaging as well as the spread of viral particles using immunofluorescence. Our analyses reveal that a single administration of oncolytic virus-loaded NSCs allows for up to 31% coverage of intracranial tumors. Such results provide valuable insights into the therapeutic potential of this novel viral delivery platform.
Insights
Neural stem cells (NSCs) loaded with oncolytic adenovirus show potential for treating malignant glioma by reaching tumor margins. A single treatment achieved up to 31% tumor coverage, offering insights into this novel therapy.
Area of Science:
- Neuro-oncology
- Gene therapy
- Stem cell biology
Background:
- Malignant glioma treatment remains challenging.
- Neural stem cell (NSC)-based delivery of oncolytic viruses shows promise.
- Understanding virus distribution after NSC transplantation is crucial for therapeutic success.
Purpose of the Study:
- To evaluate the tumor coverage potential of oncolytic adenovirus delivered by NSCs.
- To assess the spatial distribution of virus-loaded NSCs in a preclinical glioma model.
Main Methods:
- Established patient-derived GBM43 human glioma xenografts in athymic nude mice.
- Administered NSCs loaded with conditionally replicating oncolytic adenovirus (NSC-CRAd-S-pk7).
- Utilized magnetic resonance (MR) imaging and 3D reconstruction of ex vivo tissue for NSC distribution analysis.
- Employed immunofluorescence to visualize viral particle spread.
Main Results:
- Unmodified NSCs and NSC-CRAd-S-pk7 showed similar distribution patterns, primarily at tumor margins.
- T2-weighted MR imaging visualized NSC accumulation at tumor sites.
- Immunofluorescence confirmed the spread of viral particles.
- A single administration of virus-loaded NSCs achieved up to 31% intracranial tumor coverage.
Conclusions:
- NSC-CRAd-S-pk7 demonstrates significant tumor coverage potential in preclinical glioma models.
- The study provides valuable insights into the therapeutic efficacy of NSC-mediated oncolytic adenovirus delivery.
- This novel viral delivery platform holds promise for malignant glioma treatment.
