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Int J Clin Exp Med. 2015 Sep 15;8(9):15840-5. eCollection 2015.

Therapeutic effects of bone marrow mesenchymal stem cells expressing interleukin-12 in mice bearing malignant ascites tumor.

Author information

1
School of Medicine, Yan'an University Yan'an 716000, Shaanxi, China.
2
Department of Otolaryngology, The Affiliated Hospital of Yan'an University Yan'an 716000, Shaanxi, China.
3
School of Life Science, Southwest University of Science and Technology Mianyang 621010, Sichuan, China ; State Key Laboratory of Biotherapy, West China Hospital, Sichuan University Chengdu 610041, Sichuan, China.

Abstract

This study is to investigate the therapeutic effects of bone marrow mesenchymal stem cells (BMSCs) expressing interleukin (IL)-12 on malignant ascites tumor-bearing mice and the related mechanisms. Malignant ascites tumor mouse model was established by the intraperitoneal inoculation with MethA or H22 tumor cells. Mouse BMSCs were transfected with lentiviral vector containing IL-12, and then transplanted into these mouse models via intraperitoneal injection. The peritoneal permeability in these mice was evaluated and compared. The contents of INF-γ and VEGF in ascites were determined by ELISA. Mouse models receiving IL-12-expressing BMSCs were rechallenged with tumor cells, and the animal survival was observed and analyzed. In both MethA and H22 tumor cell-induced malignant ascites tumor mouse models, there were no significant differences in the peritoneal permeability between the normal saline (NS), BMSC-control, and BMSC-null groups. However, compared with NS control group, the peritoneal permeability was significantly decreased by IL-12-expressing BMSCs. Moreover, ELISA showed that, in both the MethA and H22 tumor cell-induced mouse models, compared with the NS control group, the contents of INF-γ in ascites were significantly elevated, while the contents of VEGF in ascites were significantly decreased, in the BMSC-IL-12 groups. In addition, IL-12-expressing BMSCs significantly elongated the survival of mouse models after rechallenging with tumor cells. IL-12-expressing BMSCs exert protective effects against malignant ascites tumor, and the anti-tumor effects might be associated with the enhanced anti-tumor immunity. Our findings might bring new insights into the treatment of tumors with immunotherapy.

KEYWORDS:

Bone marrow mesenchymal stem cells (BMSCs); immunotherapy; interleukin (IL)-12; malignant ascites tumor

PMID:
26629085
PMCID:
PMC4658974

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