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Mesenchymal Stem Cells: Potential Precursors for Tumor Stroma and Targeted-Delivery Vehicles for Anticancer Agents

Background: High concentrations of interferon beta (IFN-β) inhibit malignant cell growth in vitro. However, the therapeutic utility of IFN-β in vivo is limited by its excessive toxicity when administered systemically at high doses. Mesenchymal stem cells (MSC) can be used to target delivery of agent...

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Published in:JNCI : Journal of the National Cancer Institute 2004-11, Vol.96 (21), p.1593-1603
Main Authors: Studeny, Matus, Marini, Frank C., Dembinski, Jennifer L., Zompetta, Claudia, Cabreira-Hansen, Maria, Bekele, Benjamin Nebiyou, Champlin, Richard E., Andreeff, Michael
Format: Article
Language:English
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Summary:Background: High concentrations of interferon beta (IFN-β) inhibit malignant cell growth in vitro. However, the therapeutic utility of IFN-β in vivo is limited by its excessive toxicity when administered systemically at high doses. Mesenchymal stem cells (MSC) can be used to target delivery of agents to tumor cells. We tested whether MSC can deliver IFN-β to tumors, reducing toxicity. Methods: Human MSC were transduced with an adenoviral expression vector carrying the human IFN-β gene (MSC-IFN-β cells). Flow cytometry was used to measure tumor cell proliferation among in vitro co-cultures of MSC-IFN-β cells and human MDA 231 breast carcinoma cells or A375SM melanoma cells. We used a severe combined immunodeficiency mouse xenograft model (4–10 mice per group) to examine the effects of injected MSC-IFN-β cells and human recombinant IFN-β on the growth of MDA 231- and A375SM-derived pulmonary metastases in vivo and on survival. All statistical tests were two-sided. Results: Co-culture of MSC-IFN-β cells with A375SM cells or MDA 231 cells inhibited tumor cell growth as compared with growth of the tumor cells cultured alone (differences in mean percentage of control cell growth: −94.0% [95% confidence interval {CI} = −81.2% to −106.8%; P
ISSN:0027-8874
1460-2105
DOI:10.1093/jnci/djh299