BACKGROUND: Mesenchymal stem cells (MSC) are widely investigated for cell therapy purposes as support of hematopoietic cell transplantation, skeletal tissue regeneration, or as a cell delivery system of therapeutic agents in cancer. However, because of their immunosuppressive capacities, we investigated the effect of MSC on the development of syngeneic tumors. METHODS: The murine MSC line C3H10T1/2 was coinjected with the Renca adenocarcinoma or the B16 melanoma cell lines in BALB/c mice. RESULTS: The injection of MSC permitted the growth of the allogeneic B16 tumor cells and reduced the delay of tumor appearance when Renca cells were implanted, without modifying the kinetics of tumor growth. This effect was observed even with a low ratio of cancer cells, mimicking minimal residual disease. In this last case, no MSC were detected in the tumor mass, suggesting that cell contact was not necessary. The presence of MSC did not enhance the development of lung metastasis after systemic injection of Renca cells. Because the proliferative rate of Renca cells was not affected by in vitro coculture with MSC, this observation is likely due to a systemic suppressive effect on the host immune system. CONCLUSIONS: Altogether, these data suggest that MSC did not interfere with the kinetics of tumor development but may reduce the delay for tumor occurrence. An important finding of this study is that a low but relevant amount of MSC may induce tumor rejection.
BACKGROUND: Mesenchymal stem cells (MSC) are widely investigated for cell therapy purposes as support of hematopoietic cell transplantation, skeletal tissue regeneration, or as a cell delivery system of therapeutic agents in cancer. However, because of their immunosuppressive capacities, we investigated the effect of MSC on the development of syngeneic tumors. METHODS: The murine MSC line C3H10T1/2 was coinjected with the Renca adenocarcinoma or the B16 melanoma cell lines in BALB/c mice. RESULTS: The injection of MSC permitted the growth of the allogeneic B16 tumor cells and reduced the delay of tumor appearance when Renca cells were implanted, without modifying the kinetics of tumor growth. This effect was observed even with a low ratio of cancer cells, mimicking minimal residual disease. In this last case, no MSC were detected in the tumor mass, suggesting that cell contact was not necessary. The presence of MSC did not enhance the development of lung metastasis after systemic injection of Renca cells. Because the proliferative rate of Renca cells was not affected by in vitro coculture with MSC, this observation is likely due to a systemic suppressive effect on the host immune system. CONCLUSIONS: Altogether, these data suggest that MSC did not interfere with the kinetics of tumor development but may reduce the delay for tumor occurrence. An important finding of this study is that a low but relevant amount of MSC may induce tumor rejection.
Authors: Jaime F Modiano; Beth A Lindborg; Ron T McElmurry; Mitzi Lewellen; Colleen L Forster; Edward A Zamora; Jerome Schaack; Donald Bellgrau; Timothy D O'Brien; Jakub Tolar Journal: Cancer Immunol Immunother Date: 2015-08-07 Impact factor: 6.968
Authors: Daniel J Weiss; Ivan Bertoncello; Zea Borok; Carla Kim; Angela Panoskaltsis-Mortari; Susan Reynolds; Mauricio Rojas; Barry Stripp; David Warburton; Darwin J Prockop Journal: Proc Am Thorac Soc Date: 2011-06