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Three-dimensional assessment of bystander effects of mesenchymal stem cells carrying a cytosine deaminase gene on glioma cells.

Jung, JH | Kim, AA | Chang, DY  | Park, YR | Suh-Kim, H  | Kim, SS
American journal of cancer research, 5(9). : 2686-2696, 2015
Journal Title
American journal of cancer research
Stem cells carrying a suicide gene have emerged as therapeutic candidates for their cytotoxic bystander effects on neighboring cancers, while being non-toxic to other parts of the body. However, traditional cytotoxicity assays are unable to adequately assess the therapeutic effects of bystander cells. Here, we report a method to assess bystander effects of therapeutic stem cells against 3-dimensionally grown glioma cells in real time. U87 glioma cells were stably transduced to express a green fluorescence protein and co-cultivated with mesenchymal stem cells engineered to carry a bacterial cytosine deaminase gene (MSC/CD). Following addition of a 5-fluorocytine (5-FC) prodrug to the co-culture, fluorescence from U87 cells was obtained and analyzed in real time. Notably, the IC50 of 5-FC was higher when U87 cells were grown 3-dimensionally in soft agar medium for 3 weeks, as compared to those grown for one week in two-dimensional monolayer cultures. Additionally, more MSC/CD cells were required to maintain a similar level of efficacy. Since three-dimensional growth of glioma cells under our co-culture condition mimics the long-term expansion of cancer cells in vivo, our method can extend to an in vitro assay system to assess stem cell-mediated anti-cancer effects before advancing into preclinical animal studies.

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Journal Papers > School of Medicine / Graduate School of Medicine > Anatomy
Ajou Authors
김, 성수  |  서, 해영  |  장, 다영
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