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Journal of Immunology Research
Volume 2014, Article ID 318098, 9 pages
http://dx.doi.org/10.1155/2014/318098
Research Article

IFN-γ-Secreting-Mesenchymal Stem Cells Exert an Antitumor Effect In Vivo via the TRAIL Pathway

1Department of Gynecology and Obstetrics, First Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an 710061, China
2Kingmed College of Laboratory Medicine, Guangzhou Medical University, Guangzhou 510182, China
3Department of Gastrointestinal-Pancreatic Surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 51800, China

Received 10 March 2014; Revised 5 May 2014; Accepted 5 May 2014; Published 26 May 2014

Academic Editor: Yi Zhang

Copyright © 2014 Xinyuan Yang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Mesenchymal stem cells (MSCs) can exhibit either prooncogenic or antitumor properties depending on the context. Based on our previous study, we hypothesized that MSCs engineered to deliver IFN- would kill cancer cells through persistent activation of the TRAIL pathway. Human bone-marrow (BM-) derived MSCs were isolated, amplified, and transduced with a lentiviral vector encoding the IFN- gene under the control of the EF1 promoter. The IFN- -modified MSCs effectively secreted functional IFN- , which led to long-term expression of TRAIL. More importantly, the IFN- -modified MSCs selectively induced apoptosis in lung tumor cells through caspase-3 activation within the target cells. The percentage of activated-caspase-3-positive tumor cells in IFN- -modified MSCs cocultures was significantly higher than in control MSCs cocultures. Treatment with anti-TRAIL antibody dramatically suppressed the caspase-3 activation observed in H460 cells. After injection into nude mice, the IFN- -modified MSCs inhibited the growth and progression of lung carcinoma compared with control cells. Collectively, our results provide a new strategy for tumor therapy that utilizes IFN- -modified MSCs.