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Intranasal Delivery of Mesenchymal Stem Cells Significantly Extends Survival of Irradiated Mice with Experimental Brain Tumors

Balyasnikova, Irina V ; Prasol, Melanie S ; Ferguson, Sherise D ; Han, Yu ; Ahmed, Atique U ; Gutova, Margarita ; Tobias, Alex L ; Mustafi, Devkumar ; Rincón, Esther ; Zhang, Lingjiao ; Aboody, Karen S ; Lesniak, Maciej S

Molecular therapy, 2014-01, Vol.22 (1), p.140-148 [Periódico revisado por pares]

United States: Elsevier Inc

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Título:
Intranasal Delivery of Mesenchymal Stem Cells Significantly Extends Survival of Irradiated Mice with Experimental Brain Tumors
Autor: Balyasnikova, Irina V ; Prasol, Melanie S ; Ferguson, Sherise D ; Han, Yu ; Ahmed, Atique U ; Gutova, Margarita ; Tobias, Alex L ; Mustafi, Devkumar ; Rincón, Esther ; Zhang, Lingjiao ; Aboody, Karen S ; Lesniak, Maciej S
Assuntos: Animals ; Apoptosis ; Brain cancer ; Brain Neoplasms - mortality ; Brain Neoplasms - pathology ; Brain Neoplasms - therapy ; Cell Line, Tumor ; Cell Movement ; Cell Tracking ; Chemokine CXCL12 - genetics ; Disease Models, Animal ; Gamma Rays ; Gene Expression ; Glioma - mortality ; Glioma - pathology ; Glioma - therapy ; Humans ; Ligands ; Magnetic Resonance Imaging ; Medical prognosis ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stromal Cells - metabolism ; Mice ; Organometallic Compounds ; Original ; Oxyquinoline - analogs & derivatives ; Radiation ; Stem cells ; Surgery ; TNF-Related Apoptosis-Inducing Ligand - genetics ; TNF-Related Apoptosis-Inducing Ligand - metabolism ; Tumors ; Xenograft Model Antitumor Assays
É parte de: Molecular therapy, 2014-01, Vol.22 (1), p.140-148
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SourceType-Scholarly Journals-1
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Descrição: Treatment options of glioblastoma multiforme are limited due to the blood–brain barrier (BBB). In this study, we investigated the utility of intranasal (IN) delivery as a means of transporting stem cell–based antiglioma therapeutics. We hypothesized that mesenchymal stem cells (MSCs) delivered via nasal application could impart therapeutic efficacy when expressing TNF-related apoptosis-inducing ligand (TRAIL) in a model of human glioma. 111In-oxine, histology and magnetic resonance imaging (MRI) were utilized to track MSCs within the brain and associated tumor. We demonstrate that MSCs can penetrate the brain from nasal cavity and infiltrate intracranial glioma xenografts in a mouse model. Furthermore, irradiation of tumor-bearing mice tripled the penetration of 111In-oxine–labeled MSCs in the brain with a fivefold increase in cerebellum. Significant increase in CXCL12 expression was observed in irradiated xenograft tissue, implicating a CXCL12-dependent mechanism of MSCs migration towards irradiated glioma xenografts. Finally, MSCs expressing TRAIL improved the median survival of irradiated mice bearing intracranial U87 glioma xenografts in comparison with nonirradiated and irradiated control mice. Cumulatively, our data suggest that IN delivery of stem cell–based therapeutics is a feasible and highly efficacious treatment modality, allowing for repeated application of modified stem cells to target malignant glioma.
Editor: United States: Elsevier Inc
Idioma: Inglês

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Intranasal Delivery of Mesenchymal Stem Cells Significantly Extends Survival of Irradiated Mice with Experimental Brain Tumors

Balyasnikova, Irina V ; Prasol, Melanie S ; Ferguson, Sherise D ; Han, Yu ; Ahmed, Atique U ; Gutova, Margarita ; Tobias, Alex L ; Mustafi, Devkumar ; Rincón, Esther ; Zhang, Lingjiao ; Aboody, Karen S ; Lesniak, Maciej S

United States: Elsevier Inc

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