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Intranasal Oncolytic Virotherapy with CXCR4-Enhanced Stem Cells Extends Survival in Mouse Model of Glioma.

Abstract
The challenges to effective drug delivery to brain tumors are twofold: (1) there is a lack of non-invasive methods of local delivery and (2) the blood-brain barrier limits systemic delivery. Intranasal delivery of therapeutics to the brain overcomes both challenges. In mouse model of malignant glioma, we observed that a small fraction of intranasally delivered neural stem cells (NSCs) can migrate to the brain tumor site. Here, we demonstrate that hypoxic preconditioning or overexpression of CXCR4 significantly enhances the tumor-targeting ability of NSCs, but without altering their phenotype only in genetically modified NSCs. Modified NSCs deliver oncolytic virus to glioma more efficiently and extend survival of experimental animals in the context of radiotherapy. Our findings indicate that intranasal delivery of stem cell-based therapeutics could be optimized for future clinical applications, and allow for safe and repeated administration of biological therapies to brain tumors and other CNS disorders.
AuthorsMahua Dey, Dou Yu, Deepak Kanojia, Gina Li, Madina Sukhanova, Drew A Spencer, Katatzyna C Pituch, Lingjiao Zhang, Yu Han, Atique U Ahmed, Karen S Aboody, Maciej S Lesniak, Irina V Balyasnikova
JournalStem cell reports (Stem Cell Reports) Vol. 7 Issue 3 Pg. 471-482 (09 13 2016) ISSN: 2213-6711 [Electronic] United States
PMID27594591 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
CopyrightCopyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.
Chemical References
  • Biomarkers
  • Chemokine CXCL12
  • Receptors, CXCR4
Topics
  • Administration, Intranasal
  • Animals
  • Biomarkers
  • Cell Line, Tumor
  • Cell Movement
  • Chemokine CXCL12 (metabolism)
  • Disease Models, Animal
  • Gene Expression
  • Genetic Therapy
  • Genetic Vectors (administration & dosage, genetics)
  • Glioma (genetics, mortality, pathology, therapy)
  • Humans
  • Hypoxia (metabolism)
  • Mice
  • Neural Stem Cells (metabolism)
  • Oncolytic Virotherapy
  • Oncolytic Viruses (genetics)
  • Phenotype
  • Receptors, CXCR4 (genetics, metabolism)
  • Stem Cell Transplantation
  • Transduction, Genetic
  • Virus Replication
  • Xenograft Model Antitumor Assays

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