IFNα-Expressing Amniotic Fluid-Derived Mesenchymal Stem Cells Migrate to and Suppress HeLa Cell-Derived Tumors in a Mouse Model
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...
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| Format: | Article |
| Language: | English |
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Wiley
2018-01-01
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| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2018/1241323 |
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| _version_ | 1849407724959301632 |
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| author | Jun Zhou Tian Liang Dejun Wang Liru Li Yan Cheng Qiuyan Guo Guangmei Zhang |
| author_facet | Jun Zhou Tian Liang Dejun Wang Liru Li Yan Cheng Qiuyan Guo Guangmei Zhang |
| author_sort | Jun Zhou |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-47854294b9af402fb3edb2ab6484ffb1 |
| institution | Kabale University |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-47854294b9af402fb3edb2ab6484ffb12025-08-20T03:35:58ZengWileyStem Cells International1687-966X1687-96782018-01-01201810.1155/2018/12413231241323IFNα-Expressing Amniotic Fluid-Derived Mesenchymal Stem Cells Migrate to and Suppress HeLa Cell-Derived Tumors in a Mouse ModelJun Zhou0Tian Liang1Dejun Wang2Liru Li3Yan Cheng4Qiuyan Guo5Guangmei Zhang6The First Affiliated Hospital of Harbin Medical University, Harbin, ChinaThe First Affiliated Hospital of Harbin Medical University, Harbin, ChinaThe First Affiliated Hospital of Harbin Medical University, Harbin, ChinaThe Third Affiliated Hospital of Harbin Medical University, Harbin, ChinaThe First Affiliated Hospital of Harbin Medical University, Harbin, ChinaThe First Affiliated Hospital of Harbin Medical University, Harbin, ChinaThe First Affiliated Hospital of Harbin Medical University, Harbin, ChinaBackground. 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.http://dx.doi.org/10.1155/2018/1241323 |
| spellingShingle | Jun Zhou Tian Liang Dejun Wang Liru Li Yan Cheng Qiuyan Guo Guangmei Zhang IFNα-Expressing Amniotic Fluid-Derived Mesenchymal Stem Cells Migrate to and Suppress HeLa Cell-Derived Tumors in a Mouse Model Stem Cells International |
| title | IFNα-Expressing Amniotic Fluid-Derived Mesenchymal Stem Cells Migrate to and Suppress HeLa Cell-Derived Tumors in a Mouse Model |
| title_full | IFNα-Expressing Amniotic Fluid-Derived Mesenchymal Stem Cells Migrate to and Suppress HeLa Cell-Derived Tumors in a Mouse Model |
| title_fullStr | IFNα-Expressing Amniotic Fluid-Derived Mesenchymal Stem Cells Migrate to and Suppress HeLa Cell-Derived Tumors in a Mouse Model |
| title_full_unstemmed | IFNα-Expressing Amniotic Fluid-Derived Mesenchymal Stem Cells Migrate to and Suppress HeLa Cell-Derived Tumors in a Mouse Model |
| title_short | IFNα-Expressing Amniotic Fluid-Derived Mesenchymal Stem Cells Migrate to and Suppress HeLa Cell-Derived Tumors in a Mouse Model |
| title_sort | ifnα expressing amniotic fluid derived mesenchymal stem cells migrate to and suppress hela cell derived tumors in a mouse model |
| url | http://dx.doi.org/10.1155/2018/1241323 |
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