tailieunhanh - Baculoviral vector loaded mesenchymal stem cells as efficient gene therapy tools for cancer treatment

Insufficient targeting of the therapeutic genes to tumor cells is one of the major reasons for failure in cancer gene therapy. Mesenchymal stem cells (MSCs) seem to be a good candidate as a carrier for gene therapy because of its selective tumor tissue-homing properties. | Turkish Journal of Biology Turk J Biol (2016) 40: 1121-1128 © TÜBİTAK doi: Research Article Baculoviral vector loaded mesenchymal stem cells as efficient gene therapy tools for cancer treatment 1 1, 2 2 Sedef Hande AKTAŞ , Hakan AKBULUT *, Ayşe Eser ELÇİN , Mahmut PARMAKSIZ , 3 4 2 1 Arzu Aktan KESKİN , Arzu ÇÖLERİ CİHAN , Yaşar Murat ELÇİN , Fikri İÇLİ 1 Department of Medical Oncology, Ankara University School of Medicine, Ankara, Turkey 2 Tissue Engineering, Biomaterials and Nanobiotechnology Laboratory, Ankara University Faculty of Science, and Ankara University Stem Cell Institute, Ankara, Turkey 3 Department of Physiology, Gazi University, Ankara, Turkey 4 Department of Biology, Ankara University Faculty of Science, Ankara, Turkey Received: Accepted/Published Online: Final Version: Abstract: Insufficient targeting of the therapeutic genes to tumor cells is one of the major reasons for failure in cancer gene therapy. Mesenchymal stem cells (MSCs) seem to be a good candidate as a carrier for gene therapy because of its selective tumor tissue-homing properties. In the current study, we constructed baculoviral vectors (BVs) carrying cytosine deaminase (CD) (BV-CD) or green fluorescence protein (GFP) genes (BV-GFP) and tested the transduction efficiency of the vectors in tumor and mesenchymal stem cells. We also tested the in vivo efficacy of the BV-CD vector in a colon cancer model. Our results showed that the recombinant baculoviral vectors can efficiently transduce mammalian cells and express genes of interest. The BV-CD vector treatment caused significant in vitro cytotoxicity when used with 5-fluorocytosine. MSCs loaded with the BV-CD vector caused a significant delay in tumor growth and increased survival when compared to control and MSC alone treated groups bearing colon cancer. Our results show that the recombinant BV-CD vector could be used either alone .

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