Gene therapy of gastric cancer using LIGHT-secreting human umbilical cord blood-derived mesenchymal stem cells

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• 作者：Xinhong Zhu (1)
  Dongming Su (2)
  Shiying Xuan (3)
  Guiliang Ma (4)
  Zhenbo Dai (5)
  Tongyun Liu (4)
  Dongqi Tang (6)
  Weizheng Mao (4)
  Chenfang Dong (7)
  
• 关键词：LIGHT (TNFSF14) ; Gastric cancer ; Lentiviral vector ; Umbilical cord blood mesenchymal stem cells (UCB ; MSCs)
• 刊名：Gastric Cancer
• 出版年：2013
• 出版时间：April 2013
• 年：2013
• 卷：16
• 期：2
• 页码：155-166
• 全文大小：1,291 KB
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• 作者单位：Xinhong Zhu (1)
  Dongming Su (2)
  Shiying Xuan (3)
  Guiliang Ma (4)
  Zhenbo Dai (5)
  Tongyun Liu (4)
  Dongqi Tang (6)
  Weizheng Mao (4)
  Chenfang Dong (7)
  
  1. Department of Central Laboratory, Qingdao Municipal Hospital, Qingdao, China
  2. Center of Metabolic Disease Research, Nanjing Medical University, Nanjing, China
  3. Department of Gastroenterology, Qingdao Municipal Hospital, Qingdao, China
  4. Department of General Surgery, Qingdao Municipal Hospital, 5 Donghai Middle Road, Qingdao, 266071, China
  5. Endoscopy Department, Tianjin Medical University Affiliated Cancer Hospital, Tianjin, China
  6. Department of Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL, 32610-0275, USA
  7. Department of Molecular and Cellular Biochemistry, Markey Cancer Center, University of Kentucky School of Medicine, BBSRB Room B336, 741 South Limestone, Lexington, KY, 40506-0509, USA
  
• ISSN：1436-3305

文摘

Background Mesenchymal stem cells (MSCs) have the ability to migrate into tumors and therefore are potential vehicles for the therapy of malignant diseases. In this study, we investigated the use of umbilical cord blood mesenchymal stem cells (UCB-MSCs) as carriers for a constant source of transgenic LIGHT (TNFSF14) to target tumor cells in vivo. Methods Lentiviral vectors carrying LIGHT genes were constructed, producing viral particles with a titer of 2?×?108?TU/L. Fourteen days after UCB-MSCs transfected by LIGHT gene packaged lentivirus had been injected into mouse gastric cancer models, the expression levels of LIGHT mRNA and protein were detected by reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). Then the tumors-approximate volumes were measured. Results The treatment with MSC-LIGHT demonstrated a strong suppressive effect on tumor growth compared to treatment with MSC and NaCl (p?<?0.001). Examination of pathological sections of the tumor tissues showed that the areas of tumor necrocis in the MSC-LIGHT group were larger than those in the MSC group. Moreover, we found that MSCs with LIGHT were able to significantly induce apoptosis of tumor cells. The expression levels of LIGHT mRNA and protein were significantly higher in the UCB-MSCs with the LIGHT gene than the levels in UCB-MSCs (p?<?0.001). Conclusion These results suggest that UCB-MSCs carrying the LIGHT gene have the potential to be used as effective delivery vehicles in the treatment of gastric cancers.