{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T13:54:09Z","timestamp":1770126849006,"version":"3.49.0"},"reference-count":43,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2012,12,21]],"date-time":"2012-12-21T00:00:00Z","timestamp":1356048000000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Gene Medicine"],"published-print":{"date-parts":[[2012,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Engineered mesenchymal stromal cells (MSC) have been used in many preclinical studies of gene directed enzyme\/prodrug therapy. We aimed to compare the efficacy of two most frequently used systems, as well as evaluate the extent of a bystander effect mediated by therapeutic MSC towards cell lines derived from different tumours.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Two approaches were compared: (i) herpes simplex virus thymidine kinase (TK)\/ganciclovir (GCV) and (ii) yeast cytosine deaminase fused with uracil phosphoribosyltransferase (CD::UPRT)\/5\u2010fluorocytosine (5\u2010FC). The cytotoxic effect mediated by therapeutic MSC was evaluated in direct co\u2010culture by a fluorimetric assay. The expression profile of tumour cells was analyzed by a quantitative polymerase chain reaction, and the ability of gap\u2010junctional intercellular communication (GJIC) was evaluated by a dye transfer assay.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Both systems were effective only on glioblastoma cells (8\u2010MG\u2010BA). The CD::UPRT\u2010MSC\/5\u2010FC system showed efficiency on melanoma A375 cells. We decreased the sensitivity of 8\u2010MG\u2010BA cells and A375 cells to the CD::UPRT\u2010MSC\/5\u2010FC system by pharmacological inhibition of thymidylate synthase, and we achieved a similar result in A375 cells by inhibition of thymidine phosphorylase. Although we demonstrated functional GJIC in A375 cells, TK\u2010MSC were ineffective in mediating the bystander effect similarly to HeLa cells, which were also relatively resistant to CD::UPRT\u2010MSC\/5\u2010FC treatment. TK\u2010MSC\/GCV treatment had a strong cytotoxic effect on MDA\u2010MB\u2010231 cells (breast carcinoma), whereas CD::UPRT\u2010MSC\/5\u2010FC treatment failed as a result of overexpression of the gene for ABCC11. Transfection of the MDA\u2010MB\u2010231 cell line with small interference RNA specific to ABCC11 led to a significantly increased sensitivity to the CD::UPRT\u2010MSC\/5\u2010FC approach.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>GJIC, expression of enzymes involved in drug metabolism and ABC transporters correlate with the response of tumour cells to treatment by MSC\u2010expressing prodrug\u2010converting genes. Copyright \u00a9 2012 John Wiley &amp; Sons, Ltd.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jgm.2684","type":"journal-article","created":{"date-parts":[[2012,11,13]],"date-time":"2012-11-13T14:49:07Z","timestamp":1352818147000},"page":"776-787","source":"Crossref","is-referenced-by-count":24,"title":["Intrinsic properties of tumour cells have a key impact on the bystander effect mediated by genetically engineered mesenchymal stromal cells"],"prefix":"10.1002","volume":"14","author":[{"given":"Miroslava","family":"Matuskova","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Oncology Cancer Research Institute of Slovak Academy of Sciences  Bratislava Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lenka","family":"Baranovicova","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Oncology Cancer Research Institute of Slovak Academy of Sciences  Bratislava 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