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.

Immunogenomic Identification for Predicting the Prognosis of Cervical Cancer Patients

“…Increasing attention has been paid to research on immunotherapy for cervical cancer. Zhou J et al have shown that IFNα-expressing amniotic fluid-derived mesenchymal stem cells can suppress HeLa cell-derived tumors in a mouse model [ 6 ]. An HPV vaccine containing some HPV16 E7 peptides presents an anti-tumor effect in tumor-free mice [ 7 ].…”

Mesenchymal stem cells engineered by modified polyethylenimine polymer for targeted cancer gene therapy, in vitro and in vivo

“…Then, the cells attached to the upper side of the membrane were removed and the migrated cells on the lower side were stained with trypan blue and counted under an inverted microscope (five fields of view, at 10× magnification). Experiments were done in triplicate 20 …”

“…When B16F0 tumors were established, the labeled cells were injected into the mice tail vein. At different times post‐injection (up to 5 days), fluorescent imaging of isolated organs and tumors was performed using Kodak in vivo imaging system F Pro (CRI, Inc., Woburn, MA) 20,21 …”

Patient-derived xenograft models in hepatopancreatobiliary cancer

“…Mouse models are critical tools in preclinical and translational research in hepatopancreatobiliary cancer [ 1 ], including drug screening, assessment of therapeutic efficacy, identification of biomarkers, and molecular subtyping. Traditionally, immortalized cancer cell lines derived from patient tumours are used to construct mouse models to simulate tumour growth in the human body [ 2 ]. In these models, immortalized cancer cell lines are injected into immunodeficient mice subcutaneously or orthotopically [ 3 ].…”