| Autor: |
Adara Aurea dos Santos, Roberta Sessa Stilhano, Leandra Santos Baptista, Priscila Martins Andrade Denapoli, Leonardo Martins Silva, Enéas Galdini Ferrazoli, Beatriz M. Longo, Simone Bittencourt, Suely Maymone de Melo, Sang Won Han, Pricila K. Martins, Clivandir Severino da Silva, Bianca Ferrarini Zanetti, Flavia Franco da Cunha |
| Rok vydání: |
2015 |
| Předmět: |
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| Zdroj: |
Molecular Therapy. 23:S253 |
| ISSN: |
1525-0016 |
| Popis: |
Glioblastoma (GBM) is the most common and lethal primary intracranial tumor. Because GBM is highly invasive and diffusely infiltrates the brain, a complete resection of the tumor is unfeasible. The gene encoding thymidine kinase from herpes simplex virus-1 (HSV-Tk) is the most commonly used suicide gene in preclinical and clinical trials against GBM. Treating GBM with mesenchymal stem cells (MSCs) that have been modified with the HSV-Tk suicide gene has brought significant advances mainly because MSCs are chemoattracted to GBM and kill tumor cells via a bystander effect. Aiming at using this strategy in clinical trials, here we evaluated the abundantly present human adipose-tissue-derived mesenchymal stem cells (AT-MSC) to treat GBM in mouse model.AT-MSCs were prepared using a mechanical protocol to avoid contamination with animal proteins and transduced with HSV-Tk via a lentiviral vector. The U-87 glioblastoma cells cultured with AT-MSC-HSV-Tk died in the presence of 25 or 50 μM ganciclovir (GCV). U-87 glioblastoma cells injected into the brains of nude mice generated tumors larger than 3.5 mm2 after 4 weeks, but the injection of AT-MSC-HSV-Tk cells one week after the U-87 injection and treated with GCV drastically reduced tumors to smaller than 0.5 mm2. View Large Image | Download PowerPoint SlideImmunohistochemical analysis of the tumors showed the presence of AT-MSC-HSV-Tk cells only within the tumor and its vicinity, but not in other areas of the brain, indicating specific migration of AT-MSC-HSV-Tk to and interaction with tumours. View Large Image | Download PowerPoint SlideIn conclusion, the AT-MSCs are good carriers of the suicide HSV-Tk gene for the treatment of GBM, and the abundance of AT-MSCs and the easier to obtain them mechanically are strong advantages when compared to using MSCs from other tissues. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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