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

Mahua Dey, Dou Yu, Deepak Kanojia, Gina Li, Madina Sukhanova, Drew A. Spencer, Katatzyna C. Pituch, Lingjiao Zhang, Yu Han, Atique Uddin Ahmed, Karen S. Aboody, Maciej S Lesniak, Irina V Balyasnikova*

*Corresponding author for this work

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)471-482
Number of pages12
JournalStem cell reports
Volume7
Issue number3
DOIs
StatePublished - Sep 13 2016

Fingerprint

Oncolytic Virotherapy
Neural Stem Cells
Stem cells
Glioma
Cell Survival
Stem Cells
Brain Neoplasms
Tumors
Brain
Oncolytic Viruses
Biological Therapy
Blood-Brain Barrier
Radiotherapy
Drug delivery
Viruses
Phenotype
Animals
Therapeutics
Pharmaceutical Preparations
Neoplasms

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

Cite this

Dey, Mahua ; Yu, Dou ; Kanojia, Deepak ; Li, Gina ; Sukhanova, Madina ; Spencer, Drew A. ; Pituch, Katatzyna C. ; Zhang, Lingjiao ; Han, Yu ; Ahmed, Atique Uddin ; Aboody, Karen S. ; Lesniak, Maciej S ; Balyasnikova, Irina V. / Intranasal Oncolytic Virotherapy with CXCR4-Enhanced Stem Cells Extends Survival in Mouse Model of Glioma. In: Stem cell reports. 2016 ; Vol. 7, No. 3. pp. 471-482.
@article{f6a3557d051340fba79cdf9e6ecdeec6,
title = "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.",
author = "Mahua Dey and Dou Yu and Deepak Kanojia and Gina Li and Madina Sukhanova and Spencer, {Drew A.} and Pituch, {Katatzyna C.} and Lingjiao Zhang and Yu Han and Ahmed, {Atique Uddin} and Aboody, {Karen S.} and Lesniak, {Maciej S} and Balyasnikova, {Irina V}",
year = "2016",
month = "9",
day = "13",
doi = "10.1016/j.stemcr.2016.07.024",
language = "English (US)",
volume = "7",
pages = "471--482",
journal = "Stem Cell Reports",
issn = "2213-6711",
publisher = "Cell Press",
number = "3",

}

Intranasal Oncolytic Virotherapy with CXCR4-Enhanced Stem Cells Extends Survival in Mouse Model of Glioma. / Dey, Mahua; Yu, Dou; Kanojia, Deepak; Li, Gina; Sukhanova, Madina; Spencer, Drew A.; Pituch, Katatzyna C.; Zhang, Lingjiao; Han, Yu; Ahmed, Atique Uddin; Aboody, Karen S.; Lesniak, Maciej S; Balyasnikova, Irina V.

In: Stem cell reports, Vol. 7, No. 3, 13.09.2016, p. 471-482.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Intranasal Oncolytic Virotherapy with CXCR4-Enhanced Stem Cells Extends Survival in Mouse Model of Glioma

AU - Dey, Mahua

AU - Yu, Dou

AU - Kanojia, Deepak

AU - Li, Gina

AU - Sukhanova, Madina

AU - Spencer, Drew A.

AU - Pituch, Katatzyna C.

AU - Zhang, Lingjiao

AU - Han, Yu

AU - Ahmed, Atique Uddin

AU - Aboody, Karen S.

AU - Lesniak, Maciej S

AU - Balyasnikova, Irina V

PY - 2016/9/13

Y1 - 2016/9/13

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84990064125&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84990064125&partnerID=8YFLogxK

U2 - 10.1016/j.stemcr.2016.07.024

DO - 10.1016/j.stemcr.2016.07.024

M3 - Article

VL - 7

SP - 471

EP - 482

JO - Stem Cell Reports

JF - Stem Cell Reports

SN - 2213-6711

IS - 3

ER -