Gene Therapy Using TRAIL-secreting Menstrual Blood Derived Mesenchymal Stem Cells Against Glioma

Gliomas are the most common primary malignant brain tumors in humans.In recent years,the incidence and mortality of glioma are increasing in China.The prognosis of patients with malignant glioma is extremely poor because glioma is refractory to conventional therapies such as surgical resection,radiation and chemotherapy.Mesenchymal stem cell-based gene therapies provide a promising strategy for the treatment of malignant glioma because of their selective migratory ability to tumor cells.The MenSCs(Menstrual blood-derived mesenchymal stem cells),a new type of MSCs,has a wide potential therapeutic role as a cellular delivery vehicle,which includes the treatment of both primary tumors and their metastases.Soluble TRAIL(sTRAIL)contains the receptor-binding domain of TRAIL(tumor necrosis factor-released apoptosis inducing ligand),a death ligand that induces apoptosis in tumor cells.In this study,to overexpress sTRAIL,MenSCs were infected with efficient adenoviral serotype 35 vectors that had no influence on its broad multipotency and low immunophenotype.We firstly determined the glioma tropic ability of MenSCs by in vitro and in vivo migration assays.Then,we used MenSCs as a cellular vehicle for targeted delivery and local production of the biologic agent sTRAIL at the tumor site.Co-culture and Transwell experiments were used to assess the anti-tumor efficacy of sTRAIL-secreting MenSCs in vitro.Furthermore,the in vivo therapeutic efficacies of these manipulated MenSCs transplanted through intravenous injection were also determined by an established glioma tumor in a mouse xenograft model.This study provided MenSCs as a vehicle for stem cell-based glioma-targeted gene therapy.