title: Analysis of glioblastoma tumor coverage by oncolytic virus-loaded neural stem cells using MRI-based tracking and histological reconstruction.
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.
authors.affiliation: The Brain Tumor Center, Pritzker School of Medicine, The University of Chicago, Chicago, IL, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Morshed
authors.affiliation: Department of Neuroscience, City of Hope National Medical Center, Beckman Research Institute, Duarte, CA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Gutova
authors.affiliation: Northwestern Brain Tumor Institute, Robert H. Lurie Cancer Center, Chicago, IL, USA.
authors.forename: J
authors.initials: J
authors.lastname: Juliano
authors.affiliation: 1] Department of Neuroscience, City of Hope National Medical Center, Beckman Research Institute, Duarte, CA, USA [2] Division of Neurosurgery, City of Hope National Medical Center, Beckman Research Institute, Duarte, CA, USA [3] Department of Radiology, Children's Hospital of Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: M E
authors.initials: ME
authors.lastname: Barish
authors.affiliation: Northwestern Brain Tumor Institute, Robert H. Lurie Cancer Center, Chicago, IL, USA.
authors.forename: A
authors.initials: A
authors.lastname: Hawkins-Daarud
authors.affiliation: Department of Radiology, Children's Hospital of Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: D
authors.initials: D
authors.lastname: Oganesyan
authors.affiliation: Department of Radiology, Children's Hospital of Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: K
authors.initials: K
authors.lastname: Vazgen
authors.affiliation: Department of Radiology, Children's Hospital of Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: T
authors.initials: T
authors.lastname: Yang
authors.affiliation: Department of Neuroscience, City of Hope National Medical Center, Beckman Research Institute, Duarte, CA, USA.
authors.forename: A
authors.identifier: 0000000259676596
authors.initials: A
authors.lastname: Annala
authors.affiliation: The Brain Tumor Center, Pritzker School of Medicine, The University of Chicago, Chicago, IL, USA.
authors.forename: A U
authors.initials: AU
authors.lastname: Ahmed
authors.affiliation: 1] Department of Neuroscience, City of Hope National Medical Center, Beckman Research Institute, Duarte, CA, USA [2] Division of Neurosurgery, City of Hope National Medical Center, Beckman Research Institute, Duarte, CA, USA.
authors.forename: K S
authors.initials: KS
authors.lastname: Aboody
authors.affiliation: Northwestern Brain Tumor Institute, Robert H. Lurie Cancer Center, Chicago, IL, USA.
authors.forename: K R
authors.initials: KR
authors.lastname: Swanson
authors.affiliation: Department of Radiology, Children's Hospital of Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Moats
authors.affiliation: The Brain Tumor Center, Pritzker School of Medicine, The University of Chicago, Chicago, IL, USA.
authors.forename: M S
authors.initials: MS
authors.lastname: Lesniak
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001921:Brain / Q000473:pathology; D045744:Cell Line, Tumor; D058948:Cell Tracking / Q000379:methods; D004195:Disease Models, Animal; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics*; D005909:Glioblastoma / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D051379:Mice; D058953:Neural Stem Cells / Q000378:metabolism*; D050504:Oncolytic Viruses / Q000235:genetics*; D014161:Transduction, Genetic; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays