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

Jin ok Ahn, Hee woo Lee, Kyoung Won Seo, Sung keun Kang, Jeong chan Ra, Hwa young Youn

Research output: Contribution to journalArticle

26 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere74897
JournalPLoS One
Volume8
Issue number9
DOIs
StatePublished - Sep 9 2013
Externally publishedYes

Fingerprint

cisplatin
interferons
melanoma
Stem cells
Mesenchymal Stromal Cells
Heterografts
Interferons
Cisplatin
adipose tissue
stem cells
Canidae
Adipose Tissue
Tumors
Melanoma
animal models
Tissue
neoplasms
dogs
Neoplasms
Therapeutics

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

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. / Ahn, Jin ok; Lee, Hee woo; Seo, Kyoung Won; Kang, Sung keun; Ra, Jeong chan; Youn, Hwa young.

In: PLoS One, Vol. 8, No. 9, e74897, 09.09.2013.

Research output: Contribution to journalArticle

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