title: Mesenchymal stem cells display tumor-specific tropism in an RCAS/Ntv-a glioma model.
abstract: 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 bone marrow of 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 two mice without MSCs based on BLI, no tumor was found, indicating that MSC 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.
authors.affiliation: Department of Neurosurgery, The University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Tiffany
authors.initials: T
authors.lastname: Doucette
authors.forename: Ganesh
authors.initials: G
authors.lastname: Rao
authors.forename: Yuhui
authors.initials: Y
authors.lastname: Yang
authors.forename: Joy
authors.initials: J
authors.lastname: Gumin
authors.forename: Naoki
authors.initials: N
authors.lastname: Shinojima
authors.forename: B Nebiyou
authors.initials: BN
authors.lastname: Bekele
authors.forename: Wei
authors.initials: W
authors.lastname: Qiao
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Frederick F
authors.initials: FF
authors.lastname: Lang
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation; D005456:Fluorescent Dyes; D005910:Glioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007269:Injections, Intra-Arterial; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000235:genetics / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism; D013194:Staining and Labeling; D018523:Tropism / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D005456:Fluorescent Dyes; D018971:Insulin-Like Growth Factor Binding Protein 2; D010982:Platelet-Derived Growth Factor