| Background and ObjectiveTraumatic brain injury (TBI) can cause severe neurological dysfunction, there is still no effective clinical treatment can reverse the pathological process TBI. In recent years, many pre-clinical studies of stem cells transplantation have shown good results in TBI animals. Other studies suggest that NT-3 and the bio-scaffold can promote the proliferation and neuronal differentiation of neural stem cells. In this study, neural stem cells and NT-3 binding collagen scaffold were used to treat TBI rat models, and proliferation and differentiation of NSCs will be carefully observed.MethodsExperimental moderate TBI was made in adult male Sprague-Dawley rats with Feeney’s method. The rats were randomly divided into four groups:①TrkC-NSC+NT-3-collage group; ②NSC+collage group; ③NSC group;④ saline. Each group contain six rats. At 7 days after brain injury, all animals were re-anaesthetized and received transplant. The modified neurological severity score (mNSS) evaluation was performed by observers blinded to the treatments at 1,7,14, and 28 days after transplantation.18F-FDG-PET and micro-MRI examination were also performed 4 weeks post-transplantation to measure the variation of glucose metabolic activity and Structure in the brain.Atl4d after transplantation, some rats were killed for immunohistochemistry staining for GFP/bax/bcl-2/nestin/ki-67/βⅢ Tubulin.Results(1) The optimum MOI for transfection of TrkC recombinant adenovirus was 100; and the transfected TrkC gene was overexpression significantly in vitro.(2) At the 5d after Neural stem cells co-cultured with collagen scaffold in vitro, neural stem cells were adhered to the collagen scaffold and connections between cells could be seen in fluorescence microscopy and scanning electron microscopy.(3) since 14d after transplantation, TrkC-NSCs+NT-3-collagen group and NSCs+collage showed significantly better neurological recovery (lower mNSS) versus control group (p <0.05).(4) At 4 weeks after TBI, there was reduced metabolic activity in the damaged parts of brain in all groups. The metabolic activity of the damaged part was highest in the TrkC-NSCs+NT-3-collagen group. There was also a Significant difference between the NSCs+collage group and the control/NSCs-only group (p<0.05).(5) The results of immunohistochemistry:At 2 weeks after transplantation, GFP positive cells in TrkC-NSCs+NT-3-collagen group mainly distributed around the damaged part,while a small part of GFP positive cells migrated to deeper brain tissue; positive staining of bcl-2/ nestin/ki-67/βⅢ Tubulin in TrkC-NSCs+NT-3-collagen group damaged part were more than control group.ConclusionThis study demonstrated the feasibility of TrkC-NSCs and NT-3-collagen cocultivation in vitro. For moderate TBI rats, the transplantation of TrkC-NSCs+NT-3-collagen shown therapeutical effect, which may related to the promoting proliferation and differentiation functions of collagen scaffold and NT-3.Background and ObjectiveGlioblastoma multiforme (GBM) is the most common primary malignant brain tumor. Despite conventional treatment, the prognosis remain poor. Therefore, it is necessary to explore a new treatment to improve the prognosis. Immunotherapy, especially the dendritic cells (DC) vaccine therapy, is developing rapidly in recent years. We have conducted a systematic review of clinical trials. The goal of this study was to examine the efficacy and safety in terms of complications, median overall survival (mOS), median progression free survival (mPFS) and quality of life.MethodsMedline, Pubmed, CMCC, Google Scholar,Embase, Ovid, Cochrane were searched from the beginning to april 2015, tracing all the references included in the study. DC-based active immunotherapy for Glioblastoma compared the clinical efficacy of clinical trials(CT) were eligible for inclusion. Reported parameters were immune response, radiological findings, mPFS and mOS. Complications were categorized based on association with the craniotomy or with the vaccine itself.ResultsA total of 19 studies with 352 patients were included in our review. Vaccination with dendritic Cells (DCs) loaded with autologous tumor cells resulted in increased median OS in patients with recurrent GBM (71.6-138.0 wks) as well as those newly diagnosed (65.0-230.4 wks).ConclusionActive immunotherapy, specifically with autologous DCs loaded with autologous tumor Cells, seems to be both safe and feasible.The method has the potential of prolonging mOS and mPFS. More clinical trials are needed to show the potential benefits of DC-based immunotherapy. |
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