Anti-tumor effect of adipose tissue derived-mesenchymal stem cells expressing interferon-β and treatment with cisplatin in a xenograft mouse model for canine melanoma
Adipose tissue-derived mesenchymal stem cells (AT-MSCs) are attractive cell-therapy vehicles for the delivery of anti-tumor molecules into the tumor microenvironment. The innate tropism of AT-MSCs for tumors has important implications for effective cellular delivery of anti-tumor molecules, includin...
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| creator | Ahn, Jin ok Lee, Hee woo Seo, Kyoung won Kang, Sung keun Ra, Jeong chan Youn, Hwa young |
| description | Adipose tissue-derived mesenchymal stem cells (AT-MSCs) are attractive cell-therapy vehicles for the delivery of anti-tumor molecules into the tumor microenvironment. The innate tropism of AT-MSCs for tumors has important implications for effective cellular delivery of anti-tumor molecules, including cytokines, interferon, and pro-drugs. The present study was designed to determine the possibility that the combination of stem cell-based gene therapy with low-dose cisplatin would improve therapeutic efficacy against canine melanoma. The IFN-β transduced canine AT-MSCs (cAT-MSC-IFN-β) inhibited the growth of LMeC canine melanoma cells in direct and indirect in vitro co-culture systems. In animal experiments using BALB/c nude mouse xenografts, which developed by injecting LMeC cells, the combination treatment of cAT-MSC-IFN-β and low-dose cisplatin significantly reduced tumor volume compared with the other treatment groups. Fluorescent microscopic analysis with a TUNEL (terminal deoxynucleotidyl transferase-mediated nick-end labeling) assay of tumor section provided evidence for homing of cAT-MSC-IFN-β to the tumor site and revealed that the combination treatment of cAT-MSC-IFN-β with low-dose cisplatin induced high levels of cell apoptosis. These findings may prove useful in further explorations of the application of these combined approaches to the treatment of malignant melanoma and other tumors. |
| doi_str_mv | 10.1371/journal.pone.0074897 |
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The innate tropism of AT-MSCs for tumors has important implications for effective cellular delivery of anti-tumor molecules, including cytokines, interferon, and pro-drugs. The present study was designed to determine the possibility that the combination of stem cell-based gene therapy with low-dose cisplatin would improve therapeutic efficacy against canine melanoma. The IFN-β transduced canine AT-MSCs (cAT-MSC-IFN-β) inhibited the growth of LMeC canine melanoma cells in direct and indirect in vitro co-culture systems. In animal experiments using BALB/c nude mouse xenografts, which developed by injecting LMeC cells, the combination treatment of cAT-MSC-IFN-β and low-dose cisplatin significantly reduced tumor volume compared with the other treatment groups. Fluorescent microscopic analysis with a TUNEL (terminal deoxynucleotidyl transferase-mediated nick-end labeling) assay of tumor section provided evidence for homing of cAT-MSC-IFN-β to the tumor site and revealed that the combination treatment of cAT-MSC-IFN-β with low-dose cisplatin induced high levels of cell apoptosis. These findings may prove useful in further explorations of the application of these combined approaches to the treatment of malignant melanoma and other tumors.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0074897</identifier><identifier>PMID: 24040358</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adipose tissue ; Adipose Tissue - cytology ; Animals ; Anticancer properties ; Antineoplastic Agents - administration & dosage ; Apoptosis ; Body fat ; Breast cancer ; Cell culture ; Cell Cycle ; Cell Line, Tumor ; Cell Movement ; Cisplatin ; Cisplatin - administration & dosage ; Coculture Techniques ; Cytokines ; DNA nucleotidylexotransferase ; Dogs ; Drug delivery systems ; Drugs ; Female ; Fluorescence ; Gene therapy ; Genetic Therapy - methods ; Good Manufacturing Practice ; Homing ; Interferon ; Interferon-beta - metabolism ; Lentivirus - genetics ; Melanoma ; Melanoma - therapy ; Mesenchymal Stem Cell Transplantation ; Mesenchymal stem cells ; Mesenchymal Stromal Cells - cytology ; Mesenchyme ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Microscopic analysis ; Skin & tissue grafts ; Skin cancer ; Stem cell transplantation ; Stem cells ; Stem Cells - cytology ; Tropism ; Tumors ; Veterinary colleges ; Xenograft Model Antitumor Assays ; Xenografts</subject><ispartof>PloS one, 2013-09, Vol.8 (9), p.e74897-e74897</ispartof><rights>2013 Ahn et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ahn, Jin ok</au><au>Lee, Hee woo</au><au>Seo, Kyoung won</au><au>Kang, Sung keun</au><au>Ra, Jeong chan</au><au>Youn, Hwa young</au><au>Rutteman, Gerard Roel</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Anti-tumor effect of adipose tissue derived-mesenchymal stem cells expressing interferon-β and treatment with cisplatin in a xenograft mouse model for canine melanoma</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2013-09-09</date><risdate>2013</risdate><volume>8</volume><issue>9</issue><spage>e74897</spage><epage>e74897</epage><pages>e74897-e74897</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Adipose tissue-derived mesenchymal stem cells (AT-MSCs) are attractive cell-therapy vehicles for the delivery of anti-tumor molecules into the tumor microenvironment. The innate tropism of AT-MSCs for tumors has important implications for effective cellular delivery of anti-tumor molecules, including cytokines, interferon, and pro-drugs. The present study was designed to determine the possibility that the combination of stem cell-based gene therapy with low-dose cisplatin would improve therapeutic efficacy against canine melanoma. The IFN-β transduced canine AT-MSCs (cAT-MSC-IFN-β) inhibited the growth of LMeC canine melanoma cells in direct and indirect in vitro co-culture systems. In animal experiments using BALB/c nude mouse xenografts, which developed by injecting LMeC cells, the combination treatment of cAT-MSC-IFN-β and low-dose cisplatin significantly reduced tumor volume compared with the other treatment groups. Fluorescent microscopic analysis with a TUNEL (terminal deoxynucleotidyl transferase-mediated nick-end labeling) assay of tumor section provided evidence for homing of cAT-MSC-IFN-β to the tumor site and revealed that the combination treatment of cAT-MSC-IFN-β with low-dose cisplatin induced high levels of cell apoptosis. These findings may prove useful in further explorations of the application of these combined approaches to the treatment of malignant melanoma and other tumors.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24040358</pmid><doi>10.1371/journal.pone.0074897</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Adipose tissue Adipose Tissue - cytology Animals Anticancer properties Antineoplastic Agents - administration & dosage Apoptosis Body fat Breast cancer Cell culture Cell Cycle Cell Line, Tumor Cell Movement Cisplatin Cisplatin - administration & dosage Coculture Techniques Cytokines DNA nucleotidylexotransferase Dogs Drug delivery systems Drugs Female Fluorescence Gene therapy Genetic Therapy - methods Good Manufacturing Practice Homing Interferon Interferon-beta - metabolism Lentivirus - genetics Melanoma Melanoma - therapy Mesenchymal Stem Cell Transplantation Mesenchymal stem cells Mesenchymal Stromal Cells - cytology Mesenchyme Mice Mice, Inbred BALB C Mice, Nude Microscopic analysis Skin & tissue grafts Skin cancer Stem cell transplantation Stem cells Stem Cells - cytology Tropism Tumors Veterinary colleges Xenograft Model Antitumor Assays Xenografts |
| title | Anti-tumor effect of adipose tissue derived-mesenchymal stem cells expressing interferon-β and treatment with cisplatin in a xenograft mouse model for canine melanoma |
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