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

PLoS One. 2013 Sep 9;8(9):e74897. doi: 10.1371/journal.pone.0074897. eCollection 2013.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / cytology
  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Cell Cycle
  • Cell Line, Tumor
  • Cell Movement
  • Cisplatin / administration & dosage*
  • Coculture Techniques
  • Dogs
  • Female
  • Genetic Therapy / methods
  • Interferon-beta / metabolism*
  • Lentivirus / genetics
  • Melanoma / therapy*
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells / cytology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Stem Cells / cytology
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Interferon-beta
  • Cisplatin

Grant support

This research was supported by the Korean Government through a National Research Foundation of Korea Grant (number 2011-0000226) and the Seoul National University Brain Fusion Program Research Grant. The authors wish to thank the research Institute for Veterinary Science, Seoul National University, and BK21 Program for Veterinary Science. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.