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Differenziazione di astrociti da cellule staminali embrionali e loro uso come vettori di transgeni nella terapia sperimentale dei gliomi cerebrali

Carai, Andrea (2011) Differenziazione di astrociti da cellule staminali embrionali e loro uso come vettori di transgeni nella terapia sperimentale dei gliomi cerebrali. Doctoral Thesis.

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Abstract

Introduction: Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor. Despite technological achievements its prognosis remains dismal. Genetic analysis has recently emerged as a powerful research tool and has allowed the discovery of many genetic alterations found in this type of cancer. As a result, gene therapy has been proposed as a promising strategy for the treatment of GBM. Aim: We describe the differentiation of astrocytes from mouse embryonic stem cells (mESC) expressing the doxicicline inducible MDA-7/IL-24 transgene and document its anti-tumor effects in vitro and in vivo. Materials and Methods: Differentiation of astrocytes was obtained from MDA-7/IL-24 transgenic mESC and documented by morphological analysis and immonofluorescence techniques. Astrocytes were further studied to assess their ability to conditionally express the MDA-7/IL-24 transgene, to migrate towards tumor cells and to cause apoptosis in U87 human high grade glioma (HGG) cells. In vivo anti-GBM properties of transgenic astrocytes were studied in a murine orthotopic xenograft model. Results: Complete differentiation of astrocytes conditionally expressing the MDA-7/IL-24 transgene was obtained. They retained migration abilities and were able to induce apoptosis in U87 cells. A significant reduction of implanted tumor volumes was observed in vivo after treatment with astrocytes. Conclusions: ESC-derived astrocytes conditionally expressing MDA-7/IL-24 transgene show promising pro-apoptotic activity against U87 HGG cells both in vitro and in vivo. Due to the preliminary nature of our results further research is warranted to allow translation of the reported results into the clinic.

Item Type:Doctoral Thesis
ID Code:5109
Contributors:Montella, Andrea
Publisher:Universita' degli studi di Sassari
Uncontrolled Keywords:Glioblastoma, terapia genica, MDA-7/IL-24, astrociti transgenici, apoptosi
Subjects:Area 06 - Scienze mediche > MED/06 Oncologia medica
Area 06 - Scienze mediche > MED/27 Neurochirurgia
Area 05 - Scienze biologiche > BIO/16 Anatomia umana
Divisions:001 Università di Sassari > 01 Dipartimenti > Scienze biomediche
Cicli, scuole e corsi:Ciclo 23 > Scuole > Scienze biomediche > Fisiologia, farmacologia, morfologia e fisiopatologia del sistema nervoso
Deposited On:04 Apr 2011 12:52

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