title: Bone marrow-derived mesenchymal stem cells co-expressing interleukin-18 and interferon-β exhibit potent antitumor effect against intracranial glioma in rats.
abstract: Bone marrow-derived mesenchymal stem cells (BMSCs) are promising gene vehicles for cancer gene therapy. In our previous study, we reported that BMSCs expressing interleukin (IL)-18 effectively inhibit the growth of glioma in rats. In the present study, we further detected the effect of BMSCs co-expressing IL-18 and interferon (IFN)-β, both of which are immunostimulatory cytokines. BMSCs were genetically engineered to express IL-18 and IFN-β by transfection of recombinant lentivirus-mediated gene transfer. Results showed that BMSCs co-expressing the two cytokines displayed more significant inhibition effect on glioma cell growth in vitro when compared with BMSCs solely expressing IL-18 or IFN-β. Treatment of BMSCs co-expressing IL-18 and IFN-β significantly prolonged the survival and inhibited tumor growth in a rat intracranial glioma model. Furthermore, these genetically engineered BMSCs remarkably promoted cell apoptosis, antitumor cytokine production and CD4+ and CD8+ T-cell infiltration in intracranial glioma tissues than BMSCs solely expressing IL-18 or IFN-β. Results of the present study suggested that IL-18 and IFN-β had a synergistic effect on glioma inhibition. Moreover, results provided evidence that delivery of IL-18 and IFN-β by BMSCs may be an excellent and promising approach to develop an effective treatment protocol for glioma therapy.
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Gang
authors.initials: G
authors.lastname: Xu
authors.affiliation: Department of Neurosurgery, The Affiliated Zhujiang Hospital, South Medical University, Guangzhou 510282, P.R. China.
authors.forename: Yanwu
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Seng
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Gang
authors.initials: G
authors.lastname: Cui
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Jianqiang
authors.initials: J
authors.lastname: Qu
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D004195:Disease Models, Animal; D015316:Genetic Therapy; D005910:Glioma / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D006801:Humans; D016899:Interferon-beta / Q000096:biosynthesis* / Q000235:genetics; D020382:Interleukin-18 / Q000096:biosynthesis* / Q000235:genetics; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D051381:Rats
chemical_list: D020382:Interleukin-18; D016899:Interferon-beta