Gene therapy of ovarian cancer using IL-21-secreting human umbilical cord mesenchymal stem cells in nude mice

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• 作者：Yunxia Zhang (1) (2)
  Jing Wang (1)
  Mulan Ren (1)
  Miao Li (2)
  Dengyu Chen (2)
  Junsong Chen (2)
  Fangfang Shi (3)
  Xiaoying Wang (2)
  Jun Dou (1) (2)
  
• 关键词：Umbilical cord mesenchymal stem cells ; Interleukin ; 21 ; Ovarian cancer ; Gene therapy
• 刊名：Journal of Ovarian Research
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：7
• 期：1
• 全文大小：835 KB
• 作者单位：Yunxia Zhang (1) (2)
  Jing Wang (1)
  Mulan Ren (1)
  Miao Li (2)
  Dengyu Chen (2)
  Junsong Chen (2)
  Fangfang Shi (3)
  Xiaoying Wang (2)
  Jun Dou (1) (2)
  
  1. Department of Gynecology & Obstetrics, Zhongda Hospital, Medical School, Southeast University, Nanjing, 210009, China
  2. Department of Pathogenic Biology and Immunology of Medical College, Southeast University, Nanjing, 210009, China
  3. Department of Oncology, Zhongda Hospital, Southeast University, Nanjing, 210009, China
  
• ISSN：1757-2215

文摘

Background The human umbilical cord mesenchymal stem cells (hUCMSCs) have the ability to migrate into tumors and therefore have been considered as an alternative source of mesenchymal progenitors for the therapy of malignant diseases. The present study was aimed to investigate effect of hUCMSCs as vehicles for a constant source of transgenic interleukin-21 (IL-21) on ovarian cancer in vivo. Methods The hUCMSCs were engineered to express IL-21 via lentiviral vector- designated ‘hUCMSCs-LV-IL-21- and then were transplanted into SKOV3 ovarian cancer xenograft-bearing nude mice. The therapeutic efficacy and mechanisms of this procedure on ovarian cancer was evaluated. Results The isolated hUCMSCs were induced to differentiate efficiently into osteoblast and adipocyte lineages in vitro. The expressed IL-21 in the supernatant from hUCMSCs-LV-IL-21 obviously stimulated splenocyte’s proliferation. The hUCMSCs-LV-IL-21 significantly reduced SKOV3 ovarian cancer burden in mice indicated by tumor sizes compared with control mice. The expressed IL-21 not only regulated the levels of IFN-γ and TNF-α in the mouse serum but also increased the expression of NKG2D and MIC A molecules in the tumor tissues. The down regulation of β-catenin and cyclin-D1 in the tumor tissues may refer to the inhibition of SKOV3 ovarian cancer growth in mice. In addition, hUCMSCs did not form gross or histological teratomas up to 60 days posttransplantation in murine lung, liver, stomach and spleen. Conclusion These results clearly indicate a safety and usability of hUCMSCs-LV- IL-21 in ovarian cancer gene therapy, suggesting the strategy may be a promising new method for clinical treatment of ovarian cancer.