Abstract
Mesenchymal stem cells (MSCs) are a kind of adult stem cells that can be isolated easily from bone marrow, adipose tissue, umbilical cord and many other tissues. MSCs have been shown to specifically migrate to inflammatory sites, including tumors, and hold great promise as tumor-specific vectors to deliver antitumor agents. Interferon-α (IFNα) has been used in clinic to treat various types of tumors; however, because of its short half-life, significant therapeutic effects require high doses that often results in serious side effects. Here, we tested whether MSCs continuingly secreting IFNα can exert a persistent antitumor effect and eliminate the side effects associated with high clinical doses of recombinant IFNα. We found that even a small number of IFNα-secreting MSCs could potently halt B16 tumor growth in vivo. The antitumor activity of IFNα-secreting MSCs was largely abolished in immunodeficient mice, an effect largely attributed to natural killer cells and CD8+ T cells. Therefore, IFNα-secreting MSCs provide an innovative strategy for tumor therapy.
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Acknowledgements
This work was supported by grants from Scientific Innovation Project of the Chinese Academy of Science (XDA 01040107 and XDA 01040110), the Ministry of Science and Technology of China (2010CB945600 and 2011DFA30630), the National Science and Technology Project of China (31010103908 and 81273316), Shanghai Municipal Key Projects of Basic Research (12JC1409200), Shanghai Municipal Natural Science Foundation (12ZR1452600), the Knowledge Innovation Program of Shanghai Institutes for Biological Sciences and the Chinese Academy of Sciences (2012KIP202).
Author contributions
YS and YW conceived this project, designed experiments and analyzed data and prepared the manuscript; CX conceived this project, designed and performed experiments, analyzed data and prepared the manuscript; LL, QC, GC, YW, YH and YH performed experiments.
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Xu, C., Lin, L., Cao, G. et al. Interferon-α-secreting mesenchymal stem cells exert potent antitumor effect in vivo. Oncogene 33, 5047–5052 (2014). https://doi.org/10.1038/onc.2013.458
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DOI: https://doi.org/10.1038/onc.2013.458
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