Anti-tumor effects of canine adipose tissue-derived mesenchymal stromal cell-based interferon-β gene therapy and cisplatin in a mouse melanoma model

Kyoung Won Seo, Hee Woo Lee, Ye In Oh, Jin Ok Ahn, Ye Rin Koh, Seung Hyun Oh, Sung Keun Kang, Hwa Young Youn

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Background aims. Adipose tissue (AT)-derived mesenchymal stromal cells (MSC) (AT-MSC) represent a novel tool for delivering therapeutic genes to tumor cells. Interferon (IFN)-β is a cytokine with pleiotropic cellular functions, including anti-proliferative, immunomodulatory and anti-angiogenic activities. The purpose of this study was to engineer canine AT-MSC (cAT-MSC) producing IFN-β and to evaluate the anti-tumor effect of cAT-MSCIFN-β combined with cisplatin in mouse melanoma model. Methods. cAT-MSC engineered to express mouse IFN-β were generated using a lentiviral vector (cAT-MSCIFN-β) and the secreted IFN-β-induced inhibition of tumor cell growth and apoptosis on B16F10 cells was investigated in vitro prior to in vivo studies. Melanoma-bearing mouse was developed by injecting B16F10 cells subcutaneously into 6-week-old C57BL/6 mice. After 14 days, cisplatin (10 mg/kg) was injected intratumorally, and 3 days later the engineered cAT-MSC were injected subcutaneously every 3 days to death. Tumor volume and survival times were measured. Results. The combination treatment of cAT-MSCIFN-β with cisplatin was more effective in inhibiting the growth of melanoma and resulted in significantly extended survival time than both an unengineered cAT-MSCcisplatin combination group and a cisplatin-alone group. Interestingly, subcutaneously injected cAT-MSCIFN-β were migrated to tumor sites. Conclusions. Our data suggest that canine AT-MSC could serve as a powerful cell-based delivery vehicle for releasing therapeutic proteins to tumor lesions. Maximal anti-tumor effects were seen when this therapy was combined with a DNA-damaging chemotherapeutic agent. This study demonstrates the possible applicability of AT-MSC-mediated IFN-β in treating canine and human cancer patients.

Original languageEnglish (US)
Pages (from-to)944-955
Number of pages12
JournalCytotherapy
Volume13
Issue number8
DOIs
StatePublished - Jan 1 2011
Externally publishedYes

Keywords

  • adipose tissue-derived mesenchymal stromal cells
  • canine
  • cell vehicle
  • interferon-β
  • melanoma

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Genetics(clinical)
  • Cell Biology
  • Transplantation
  • Cancer Research

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