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Vol 49(2015) N 6 p. 904-911; DOI 10.1134/S0026893315060126  L.S. Krasikova1,2, S.S. Karshieva2*, I.B. Cheglakov2, A.V. Belyavsky2 Mesenchymal stem cells expressing cytosine deaminase inhibit growth of murine melanoma B16F10 in vivo 1Pushchino State Institute of Natural Sciences, Pushchino, 142290 Russia2Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia *skarshieva@gmail.com Received - 2014-12-10; Accepted - 2015-03-26 The study was aimed to estimate the efficacy of mesenchymal stem cell (MSC)-based suicide gene therapy in mice bearing murine melanoma B16F10. Mouse adipose tissue-derived MSCs were transfected with plasmid constructs to express cytosine deaminase fused with uracil phosphoribosyltransferase (CDA/UPRT) or CDA/UPRT fused with HSV-1 tegument protein VP22 (CDA/UPRT/VP22). Direct intratumoral grafting of MSCs expressing CDA/UPRT or CDA/UPRT/VP22 followed by systemic administration of 5-fluorocytosine (5-FC) was found to significantly inhibit tumor growth. The tumor volume was reduced by 53% in mice treated with CDA/UPRT-MSCs and 58% in mice treated with CDA/UPRT/VP22-MSCs as compared with control mice implanted with B16F10 melanoma. CDA/UPRT-MSC and CDA/UPRT/VP22-MSC injections increased the survival of mice bearing B16F10 melanoma by 15 and 26%, respectively. The results showed a biologically significant antitumor effect of MSCs expressing the CDA/UPRT suicide gene in the B16F10 murine melanoma model. mesenchymal stem cells, cytosine deaminase, melanoma B16F10, gene therapy |
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