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IFNα-Expressing Amniotic Fluid-Derived Mesenchymal Stem Cells Migrate to and Suppress HeLa Cell-Derived Tumors in a Mouse Model.

ABSTRACT: Background:Immunotherapy for cervical cancer with type I interferon (IFN) is limited because of the cytotoxicity that accompanies the high doses that are administered. In this study, we investigated the utilization of amniotic fluid-derived mesenchymal stem cells (AF-MSCs) as a means for delivering IFNα to local tumor sites for the suppression of cervical cancer in a mouse model using HeLa cell xenografts. Methods:The tumor tropism ability of AF-MSCs and AF-MSCs genetically modified to overexpress IFNα (IFNα-AF-MSCs) was examined through Transwell in vitro and through fluorescent images and immunohistochemistry in a mouse model. Tumor size and tumor apoptosis were observed to evaluate the efficacy of the targeting therapy. Mechanistically, tumor cell apoptosis was detected by cytometry and TUNEL, and oncogenic proteins c-Myc, p53, and Bcl-2 as well as microvessel density were detected by immunohistochemistry. Results:In this model, intravenously injected AF-MSCs selectively migrated to the tumor sites, participated in tumor construction, and promoted tumor growth. After being genetically modified to overexpress IFNα, the IFNα-AF-MSCs maintained their tumor tropism but could significantly suppress tumor growth. The restrictive efficacy of IFNα-AF-MSCs was associated with the suppression of angiogenesis, inhibition of tumor cell proliferation, and induction of apoptosis in tumor cells. Neither AF-MSCs nor IFNα-AF-MSCs trigger tumor formation. Conclusions:IFNα-AF-MSC-based therapy is feasible and shows potential for treating cervical cancer, suggesting that AF-MSCs may be promising vehicles for delivering targeted anticancer therapy.

SUBMITTER: Zhou J

PROVIDER: S-EPMC5901954 | biostudies-literature |

REPOSITORIES: biostudies-literature

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The Different Effects of IFN-<i>?</i> and IFN-<i>?</i> on the Tumor-Suppressive Activity of Human Amniotic Fluid-Derived Mesenchymal Stem Cells.

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