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

الملخص EN

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.