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.