Analysis of glioblastoma tumor coverage by oncolytic virus-loaded neural stem cells using MRI-based tracking and histological reconstruction

R. A. Morshed, M. Gutova, J. Juliano, M. E. Barish, A. Hawkins-Daarud, D. Oganesyan, K. Vazgen, T. Yang, A. Annala, A. U. Ahmed, K. S. Aboody, Kristin Swanson, R. A. Moats, M. S. Lesniak

Research output: Contribution to journalArticle

24 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)55-61
Number of pages7
JournalCancer Gene Therapy
Volume22
Issue number1
DOIs
StatePublished - Jan 28 2015
Externally publishedYes

Fingerprint

Oncolytic Viruses
Neural Stem Cells
Glioblastoma
Neoplasms
Adenoviridae
Nude Mice
Glioma
Magnetic Resonance Imaging
Stem Cell Transplantation
Virion
Fluorescent Antibody Technique
Therapeutics
Viruses
Brain

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Medicine
  • Molecular Biology
  • Medicine(all)

Cite this

Morshed, R. A., Gutova, M., Juliano, J., Barish, M. E., Hawkins-Daarud, A., Oganesyan, D., ... Lesniak, M. S. (2015). Analysis of glioblastoma tumor coverage by oncolytic virus-loaded neural stem cells using MRI-based tracking and histological reconstruction. Cancer Gene Therapy, 22(1), 55-61. https://doi.org/10.1038/cgt.2014.72

Analysis of glioblastoma tumor coverage by oncolytic virus-loaded neural stem cells using MRI-based tracking and histological reconstruction. / Morshed, R. A.; Gutova, M.; Juliano, J.; Barish, M. E.; Hawkins-Daarud, A.; Oganesyan, D.; Vazgen, K.; Yang, T.; Annala, A.; Ahmed, A. U.; Aboody, K. S.; Swanson, Kristin; Moats, R. A.; Lesniak, M. S.

In: Cancer Gene Therapy, Vol. 22, No. 1, 28.01.2015, p. 55-61.

Research output: Contribution to journalArticle

Morshed, RA, Gutova, M, Juliano, J, Barish, ME, Hawkins-Daarud, A, Oganesyan, D, Vazgen, K, Yang, T, Annala, A, Ahmed, AU, Aboody, KS, Swanson, K, Moats, RA & Lesniak, MS 2015, 'Analysis of glioblastoma tumor coverage by oncolytic virus-loaded neural stem cells using MRI-based tracking and histological reconstruction', Cancer Gene Therapy, vol. 22, no. 1, pp. 55-61. https://doi.org/10.1038/cgt.2014.72
Morshed, R. A. ; Gutova, M. ; Juliano, J. ; Barish, M. E. ; Hawkins-Daarud, A. ; Oganesyan, D. ; Vazgen, K. ; Yang, T. ; Annala, A. ; Ahmed, A. U. ; Aboody, K. S. ; Swanson, Kristin ; Moats, R. A. ; Lesniak, M. S. / Analysis of glioblastoma tumor coverage by oncolytic virus-loaded neural stem cells using MRI-based tracking and histological reconstruction. In: Cancer Gene Therapy. 2015 ; Vol. 22, No. 1. pp. 55-61.
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