Mesenchymal Stem Cells Display Tumor-Specific Tropism in an RCAS/Ntv-a Glioma Model
Bone marrow-derived mesenchymal stem cells (MSCs) have been shown to localize to gliomas and deliver therapeutic agents. However, the clinical translation of MSCs remains poorly defined because previous studies relied on glioma models with uncertain relevance to human disease, typically xenograft m...
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doaj-9a269fcfc62d4b21b5d423c7fdac2f6d2020-11-24T22:58:35ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022011-08-0113871672510.1593/neo.101680Mesenchymal Stem Cells Display Tumor-Specific Tropism in an RCAS/Ntv-a Glioma ModelTiffany Doucette0Ganesh Rao1Yuhui Yang2Joy Gumin3Naoki Shinojima4B. Nebiyou Bekele5Wei Qiao6Wei Zhang7Frederick F. Lang8Department of Neurosurgery, The University of Texas, MD Anderson Cancer Center, Houston, TX, USADepartment of Neurosurgery, The University of Texas, MD Anderson Cancer Center, Houston, TX, USADepartment of Neurosurgery, The University of Texas, MD Anderson Cancer Center, Houston, TX, USADepartment of Neurosurgery, The University of Texas, MD Anderson Cancer Center, Houston, TX, USADepartment of Neurosurgery, The University of Texas, MD Anderson Cancer Center, Houston, TX, USADepartment of Biostatistics, The University of Texas, MD Anderson Cancer Center, Houston, TX, USADepartment of Biostatistics, The University of Texas, MD Anderson Cancer Center, Houston, TX, USADepartment of Pathology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USADepartment of Neurosurgery, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA Bone marrow-derived mesenchymal stem cells (MSCs) have been shown to localize to gliomas and deliver therapeutic agents. However, the clinical translation of MSCs remains poorly defined because previous studies relied on glioma models with uncertain relevance to human disease, typically xenograft models in immunocompromised mice. To address this shortcoming, we used the RCAS/Ntv-a system, in which endogenous gliomas that recapitulate the tumor and stromal features of human gliomas develop in immunocompetent mice. MSCs were harvested from bonemarrowof Ntv-a mice and injected into the carotid artery of Ntv-a mice previously inoculated with RCAS-PDGF-B and RCAS-IGFBP2 to induce malignant gliomas (n = 9). MSCs were labeled with luciferase for in vivo bioluminescence imaging (BLI). After intra-arterial injection, BLI revealed MSCs in the right frontal lobe in seven of nine mice. At necropsy, gliomas were detected within the right frontal lobe in all these mice, correlating with the location of the MSCs. In the twomice without MSCs based on BLI, no tumor was found, indicating thatMSC localization was tumor specific. In another cohort of mice (n = 9), MSCs were labeled with SP-DiI, a fluorescent vital dye. After intra-arterial injection, fluorescence microscopy revealed SP-DiI-labeled MSCs throughout tumors 1 to 7 days after injection but not in nontumoral areas of the brain. MSCs injected intravenously did not localize to tumors (n = 12). We conclude that syngeneic MSCs are capable of homing to endogenous gliomas in immunocompetent mice. These findings support the use of MSCs as tumor-specific delivery vehicles for treating gliomas. http://www.sciencedirect.com/science/article/pii/S1476558611800060 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Tiffany Doucette Ganesh Rao Yuhui Yang Joy Gumin Naoki Shinojima B. Nebiyou Bekele Wei Qiao Wei Zhang Frederick F. Lang |
spellingShingle |
Tiffany Doucette Ganesh Rao Yuhui Yang Joy Gumin Naoki Shinojima B. Nebiyou Bekele Wei Qiao Wei Zhang Frederick F. Lang Mesenchymal Stem Cells Display Tumor-Specific Tropism in an RCAS/Ntv-a Glioma Model Neoplasia: An International Journal for Oncology Research |
author_facet |
Tiffany Doucette Ganesh Rao Yuhui Yang Joy Gumin Naoki Shinojima B. Nebiyou Bekele Wei Qiao Wei Zhang Frederick F. Lang |
author_sort |
Tiffany Doucette |
title |
Mesenchymal Stem Cells Display Tumor-Specific Tropism in an RCAS/Ntv-a Glioma Model |
title_short |
Mesenchymal Stem Cells Display Tumor-Specific Tropism in an RCAS/Ntv-a Glioma Model |
title_full |
Mesenchymal Stem Cells Display Tumor-Specific Tropism in an RCAS/Ntv-a Glioma Model |
title_fullStr |
Mesenchymal Stem Cells Display Tumor-Specific Tropism in an RCAS/Ntv-a Glioma Model |
title_full_unstemmed |
Mesenchymal Stem Cells Display Tumor-Specific Tropism in an RCAS/Ntv-a Glioma Model |
title_sort |
mesenchymal stem cells display tumor-specific tropism in an rcas/ntv-a glioma model |
publisher |
Elsevier |
series |
Neoplasia: An International Journal for Oncology Research |
issn |
1476-5586 1522-8002 |
publishDate |
2011-08-01 |
description |
Bone marrow-derived mesenchymal stem cells (MSCs) have been shown to localize to gliomas and deliver therapeutic agents. However, the clinical translation of MSCs remains poorly defined because previous studies relied on glioma models with uncertain relevance to human disease, typically xenograft models in immunocompromised mice. To address this shortcoming, we used the RCAS/Ntv-a system, in which endogenous gliomas that recapitulate the tumor and stromal features of human gliomas develop in immunocompetent mice. MSCs were harvested from bonemarrowof Ntv-a mice and injected into the carotid artery of Ntv-a mice previously inoculated with RCAS-PDGF-B and RCAS-IGFBP2 to induce malignant gliomas (n = 9). MSCs were labeled with luciferase for in vivo bioluminescence imaging (BLI). After intra-arterial injection, BLI revealed MSCs in the right frontal lobe in seven of nine mice. At necropsy, gliomas were detected within the right frontal lobe in all these mice, correlating with the location of the MSCs. In the twomice without MSCs based on BLI, no tumor was found, indicating thatMSC localization was tumor specific. In another cohort of mice (n = 9), MSCs were labeled with SP-DiI, a fluorescent vital dye. After intra-arterial injection, fluorescence microscopy revealed SP-DiI-labeled MSCs throughout tumors 1 to 7 days after injection but not in nontumoral areas of the brain. MSCs injected intravenously did not localize to tumors (n = 12). We conclude that syngeneic MSCs are capable of homing to endogenous gliomas in immunocompetent mice. These findings support the use of MSCs as tumor-specific delivery vehicles for treating gliomas.
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url |
http://www.sciencedirect.com/science/article/pii/S1476558611800060 |
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