Human menstrual blood-derived mesenchymal stem cells as a cellular vehicle for malignant glioma gene therapy
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Xiao-Jun Wang1,*, Bing-Yu Xiang1,*, Ya-Hui Ding2,5,*, Lu Chen1, Hai Zou2,5, Xiao-Zhou Mou3 and Charlie Xiang1,4
1State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
2Department of Cardiology, Zhejiang Provincial People's Hospital, Hangzhou 310014, China
3Clinical Research Institute, Zhejiang Provincial People’s Hospital, Hangzhou 310014, China
4Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310014, China
5People’s Hospital of Hangzhou Medical College, Hangzhou 310014, China
Hai Zou, email: firstname.lastname@example.org
Charlie Xiang, email: email@example.com
Xiao-Zhou Mou, email: firstname.lastname@example.org
Keywords: gene therapy, menstrual blood-derived mesenchymal stem cell (MenSC), malignant gliomas, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)
Received: January 30, 2017 Accepted: April 20, 2017 Published: May 04, 2017
Despite many advances in conventional treatment strategies, there is no effective treatment modality for malignant gliomas. Gene therapy may offer a promising option for gliomas and several gene therapy approaches have shown anti-tumor efficiency in previous studies. Mesenchymal stem cell-based gene therapies, in which stem cells are genetically engineered to express therapeutic molecules, have shown tremendous potential because of their innate homing ability. In this study, human menstrual blood-derived MSCs (MenSC), a novel type of multipotential MSCs displays tropism for human malignant glioma when used as a gene delivery vehicle for therapeutics. Secretable trimeric TRAIL (stTRAIL) contains the receptor-binding domain of TRAIL, a death ligand that induces apoptosis in tumor cells. To overexpress stTRAIL, MenSCs were infected with efficient adenoviral serotype 35 vectors that had no influence on its broad multipotency and low immunophenotype. The modified MenSCs served as an excellent local drug delivery system for tumor site-specific targeted delivery and demonstrated therapeutic efficacy in an animal xenografts tumor model of U-87 MG cells. The MenSC-stTRAIL cells induced antitumor effects in vitro by significantly increasing apoptosis (P < 0.05). It also significantly reduced tumor burden in vivo (P < 0.05). The results showed that the proliferation of tumor cells was significantly reduced (P < 0.05). The MenSC, as a cellular delivery vehicle has a wide potential therapeutic role, which includes the treatment of tumors.
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