Genetically engineered theranostic mesenchymal stem cells for the evaluation of the anticancer efficacy of enzyme/prodrug systems

作者: Faranak Salman Nouri , Xing Wang , Arash Hatefi

DOI: 10.1016/J.JCONREL.2015.01.003

关键词: PharmacologyMesenchymal stem cellCytosine deaminaseBiologySuicide geneThymidine kinaseUracil phosphoribosyltransferaseViral vectorProdrugGenetically modified organism

摘要: Over the past decade, various enzyme/prodrug systems such as thymidine kinase/ganciclovir (TK/GCV), yeast cytosine deaminase/5-fluorocytosine (yCD/5-FC) and nitroreductase/CB1954 (NTR/CB1954) have been used for stem cell mediated suicide gene therapy of cancer. Yet, no study has conducted to compare demonstrate advantages disadvantages using one system over another. Knowing that each its own strengths weaknesses, we utilized mesenchymal cells (MSCs) a medium perform first time comparative illustrated impact subtle differences among these on therapeutic outcome. For purposes, genetically modified MSCs stably express panel four genes including TK (TK007 TK(SR39) mutants), deaminase:uracil phosphoribosyltransferase (yCD:UPRT) nitroreductase (NTR). Then, evaluated anticancer efficacies engineered in vitro vivo by SKOV3 line which is sensitive all systems. In addition, were luciferase making them suitable quantitative imaging dose-response relationship studies animals. Considering limitations imposed prodrugs' bystander effects, our findings show yCD:UPRT/5-FC most effective ones tested. Our also theranostic are reliable side-by-side evaluation screening at preclinical level. The results this could help scientists who utilize cell-based, non-viral or viral vectors cancer make more informed decisions when choosing

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