Background: The human umbilical cord mesenchymal stem cells (hUCMSCs) have the ability to migrate into\r\ntumors and therefore have been considered as an alternative source of mesenchymal progenitors for the therapy\r\nof malignant diseases. The present study was aimed to investigate effect of hUCMSCs as vehicles for a constant\r\nsource of transgenic interleukin-21 (IL-21) on ovarian cancer in vivo.\r\nMethods: The hUCMSCs were engineered to express IL-21 via lentiviral vector- designated ââ?¬Ë?hUCMSCs-LV-IL-21ââ?¬â?¢, and\r\nthen were transplanted into SKOV3 ovarian cancer xenograft-bearing nude mice. The therapeutic efficacy and\r\nmechanisms of this procedure on ovarian cancer was evaluated.\r\nResults: The isolated hUCMSCs were induced to differentiate efficiently into osteoblast and adipocyte lineages in vitro.\r\nThe expressed IL-21 in the supernatant from hUCMSCs-LV-IL-21 obviously stimulated splenocyteââ?¬â?¢s proliferation. The\r\nhUCMSCs-LV-IL-21 significantly reduced SKOV3 ovarian cancer burden in mice indicated by tumor sizes compared with\r\ncontrol mice. The expressed IL-21 not only regulated the levels of IFN-? and TNF-a in the mouse serum but also\r\nincreased the expression of NKG2D and MIC A molecules in the tumor tissues. The down regulation of Ã?Ÿ-catenin and\r\ncyclin-D1 in the tumor tissues may refer to the inhibition of SKOV3 ovarian cancer growth in mice. In addition, hUCMSCs\r\ndid not form gross or histological teratomas up to 60 days posttransplantation in murine lung, liver, stomach and spleen.\r\nConclusion: These results clearly indicate a safety and usability of hUCMSCs-LV- IL-21 in ovarian cancer gene therapy,\r\nsuggesting the strategy may be a promising new method for clinical treatment of ovarian cancer.
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