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TRAIL-engineered pancreas-derived mesenchymal stem cells: characterization and cytotoxic effects on pancreatic cancer cells

Cancer Gene Therapy volume 19, pages 652–658 (2012)Cite this article

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Abstract

Mesenchymal stem cells (MSCs) have attracted great interest in cancer therapy owing to their tumor-oriented homing capacity and the feasibility of autologous transplantation. Currently, pancreatic cancer patients face a very poor prognosis, primarily due to the lack of therapeutic strategies with an effective degree of specificity. Anticancer gene-engineered MSCs specifically target tumor sites and can produce anticancer agents locally and constantly. This study was performed to characterize pancreas-derived MSCs and investigate the effects of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-engineered MSCs on pancreatic cancer cells under different culture conditions. Pancreas-derived MSCs exhibited positive expression on CD44, CD73, CD95, CD105, negative on CD34 and differentiated into adipogenic and osteogenic cells. TRAIL expression was assessed by both enzyme-linked immunosorbent assay and western blot analysis. Different patterns of TRAIL receptor expression were observed on the pancreatic cancer cell lines, including PANC1, HP62, ASPC1, TRM6 and BXPC3. Cell viability was assessed using a real-time monitoring system. Pancreatic cancer cell death was proportionally related to conditioned media from MSCnsTRAIL and MSCstTRAIL. The results suggest that MSCs exhibit intrinsic inhibition of pancreatic cancer cells and that this effect can be potentiated by TRAIL-transfection on death receptor-bearing cell types.

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Acknowledgements

This work was supported by the JDRF, the VGH and UBC Hospital Foundation and the Guangxi Ministry of Science and Technology. We also would like to extend our gratitude to Dr E LeBlanc, Ms K Frewin, Dr Melissa Brierley and Jeffrey Helm, who have been tremendous resources throughout our work. We are grateful for Mrs Crystal Robertson's assistance for manuscript editing.

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Author notes

  1. M R Moniri and X-Y Sun: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada

    M R Moniri, J Rayat, Z Ao, Z He, L-J Dai & G L Warnock

  2. Institute of Transplant Medicine, 303 Hospital of PLA, Nanning, PRC

    X-Y Sun

  3. Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada

    D Dai & C B Verchere

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  1. M R Moniri
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Correspondence to L-J Dai.

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Moniri, M., Sun, XY., Rayat, J. et al. TRAIL-engineered pancreas-derived mesenchymal stem cells: characterization and cytotoxic effects on pancreatic cancer cells. Cancer Gene Ther 19, 652–658 (2012). https://doi.org/10.1038/cgt.2012.46

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