• Human adipose tissue-derived mesenchymal stem cells inhibit melanoma growth in vitro and in vivo

    Background/Aim: The effects of adipose tissue derived mesenchymal stem cells (AT-MSCs) on the growth of human malignancies, including melanoma, are controversial and the underlying mechanisms are not yet-well understood. The aim of the present study was to investigate the in vitro and in vivo anti-tumor effects of human AT-MSCs on human melanoma.

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

    요약 :
    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-MSC – IFN- β combined with cisplatin in mouse melanoma model. Methods. cAT-MSC engineered to express mouse IFN- β were generated using a lentiviral vector (cAT-MSC – IFN- 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-MSC – IFN- β with cisplatin was more effective in inhibiting the growth of melanoma and resulted in signifi cantly extended survival time than both an unengineered cAT-MSC – cisplatin combination group and a cisplatin-alone group. Interestingly, subcutaneously injected cAT-MSC – IFN- 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 DNAdamaging chemotherapeutic agent. This study demonstrates the possible applicability of AT-MSC-mediated IFN- β in treating canine and human cancer patients

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  • 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

    요약 : 
    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-b transduced canine AT-MSCs (cAT-MSC-IFN-b) 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-b 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-b to the tumor site and revealed that the combination treatment of cAT-MSC-IFN-b 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

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