P08.54 Targeting brain tumor with mesenchymal stem cells in the experimental model of the orthotopic glioblastoma
| Autor: | L. Yakovleva, E. N. Tolkunova, Maxim Shevtsov, G. Timin, B. Nikolaev, Y. Marchenko, V. A. Ryzhov |
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| Rok vydání: | 2017 |
| Předmět: | |
| Zdroj: | Neuro-Oncology. 19:iii65-iii66 |
| ISSN: | 1523-5866 1522-8517 |
| Popis: | Introduction: Tumor tracking properties of mesenchymal stem cells (MSCs) provide an attractive opportunity for targeted suicide gene therapy of brain tumors. However, intravenously injected MSCs can accumulate in other organs, thereby contributing to plausible side effects. Therefore, in vivo MSCs biodistribution studies are of high importance. Materials and Methods: Tumor-targeting and organ biodistribution of the intravenously administered rat MSCs were assessed in the intracranial C6 rat glioma model. Cells were labeled with superparamagnetic iron oxide nanoparticles (SPIONs) that enable the visualization of MSCs using high-resolution (11T) magnetic resonance imaging (MRI). Biodistribution studies were performed using nonlinear-longitudinal-response-M2 (NLR-M2) measurements with subsequent histological analyses. Results: MSCs isolated from bone marrow of adult rats were efficiently labeled by SPIONs as was demonstrated by confocal and transmission electron microscopies. Cytotoxicity studies (i.e., MTT assay) clearly demonstrated that intracellular inclusion of nanoparticles did not affect the cell survival as well as the in vitro adipogenic, osteogenic and hondrogenic differentiation capacity. In vivo studies showed that following intravenous injection of the SPIONs-labeled MSCs in the glioma bearing animals the cells accumulated in the tumor site. On the T2-weighted MR images the cells presented as ´dark zones´ in the glioma tissue. Subsequent biodistribution analyses with the help of NLR-M2 method indicated retention of MSCs in the tumor that was further confirmed by histological assessment. Conclusions: Taken together, the presented study suggests that MSCs could be applied for noninvasive targeting and imaging of malignant brain tumors. |
| Databáze: | OpenAIRE |
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