The future of bone marrow stromal cell transplantation for the treatment of spinal cord injury

Bone marrow stromal cell （BMSC） transplantation therapy is a promising approach for treating spinal cord injury （SCI）, based on a number of experimental and clinical reports （Wright et al., 2011）. BMSCs are a source of neuroregenerative somatic stem cells that are without the potential for tumorigenicity. Although clinical studies of autologous BMSC transplantation have been reported in Asia （fiang et al., 2013; Yoon et al., 2007）, in Japan, it is currently an uncommon procedure and highly controversial as well. This perspective paper provides an overview of the clinical effectiveness of BMSC trans- 191antation and a proposal to enhance its use as a viable therapy.

Propofol promotes spinal cord injury repair by bone marrow mesenchymal stem cell transplantation

Propofol is a neuroprotective anesthetic. Whether propofol can promote spinal cord injury repair by bone marrow mesenchymal stem cells remains poorly understood. We used rats to investigate spinal cord injury repair using bone marrow mesenchymal stem cell transplantation combined with propofol administration via the tail vein. Rat spinal cord injury was clearly alleviated; a large number of newborn non-myelinated and myelinated nerve fibers appeared in the spinal cord, the numbers of CM-Dil-labeled bone marrow mesenchymal stem cells and fluorogold-labeled nerve fibers were increased and hindlimb motor function of spinal cord-injured rats was markedly improved. These improvements were more prominent in rats subjected to bone marrow mesenchymal cell transplantation combined with propofol administration than in rats receiving monotherapy. These results indicate that propofol can enhance the therapeutic effects of bone marrow mesenchymal stem cell transplantation on spinal cord injury in rats.

Brain-derived neurotrophical factor after olfactory ensheathing cells transplantation in spinal cord injury of rats

Objective To observe the expression of brain - derived neurotrophical factor ( BDNF) in injury spinal cord after transplantation olfactory ensheathing cells ( OECs) , and to investigate the mechanism of OECs repairing spinal cord injury. Methods OECs from GFP transgenic rats were separated and cultured for transplantation. Spinal cord injury rats were separated two groups by

Improvement of neurological function in rats with spinal cord injury after the transplantation of neural stem cells directly differentiated from bone marrow mesenchymal stem cells

Objective To study the effect and mechanism of neurological function recovery in rats with spinal cord injury ( SCI) rats after transplantation of neural stem cells which are directly differentiated from bone marrow mesenchymal stem cells ( BMSC ) ,and to investigate the suitable engraftment time. Methods BMSC at 3rd passage were differentiated into neural stem cells ( NSC) , and immunofluorescence staining was used to

The prospects of regenerative medicine combined with rehabilitative approaches for chronic spinal cord injury animal models

Regenerative medicine has opened a window for functional recovery in acute-to-subacute phase spinal cord injury（SCI）.By contrast,there are still only a few studies have focused on the treatment of the chronically injured spinal cord,in which cell-based regenerative medicine seems less effective.Since the majority of SCI patients are in the chronic phase,representing a major challenge for the clinical application of cellbased regenerative medicine.Although combined therapies for the treatment of chronic SCI have attracted attention of researchers and its potential importance is also widely recognized,there had been very few studies involving rehabilitative treatments to date.In a recent study,we have demonstrated for the first time that treadmill training combined with cell transplantation significantly promotes functional recovery even in chronic SCI,not only in additive but also in synergistic manner.Even though we have succeeded to outline the profiles of recovery secondary to the combination therapy,the mechanism underlying the effects remain unsolved.In this review article,we summarize the present progress and consider the prospect of the cell-based regenerative medicine particularly combined with rehabilitative approaches for chronic SCI animal models.

Locally controlled release of immunosuppressive promotes survival of transplanted adult spinal cord tissue

Transplantation of adult spinal cord tissue(aSCT)is a promising treatment for spinal cord injury(SCI)basing on various types of neural cells and matrix components inside aSCT.However,long-term systemic administration of immunosuppressors(e.g.tacrolimus,TAC)is required for the survival of allogeneic tissue,which often associated with severe side effects such as infection,liver damageand renal failure.In this study,a triglycerol monostearate(TGM)-based TAC delivery system(e.g.TAC@TGM)with high drug loading concentration was developed,which possessed injectable properties as well as sustainable and immune-responsive drug release behaviors.In complete transected SCI model,locally injected TAC@TGM could reduce the infiltration of inflammation cells,enhance the survival of transplanted aSCT(e.g.Tuj-1^(+)and NF^(+)neurons)and promote the recovery of locomotor function.Moreover,controlled release of TAC by TAC@TGM attenuated side effects of TAC on liver and kidneys compared with traditional systemic administration.More importantly,the developed TAC@TGM system provided a facile single dose of long-term immunosuppressive effect not just for aSCT transplantation,but also for other tissue/organ and cell transplantations.

Influence of patients' age on functional recovery after transplantation of olfactory ensheathing cells into injured spinal cord injury

Objective To evaluate the restoration of function after spinal cord injury (SCI) in patients of different ages who have underwent intraspinal transplantation of olfactory ensheathing cells (OECs). Methods One hundred and seventy-one SCI patients were included in this study. Of them,139 were male and 32 were female,with age ranging from 2 to 64 years (mean,34.9 years). In all SCI patients the lesions were injected at the time of operation with OECs. According to their ages,the patients were divided into 5 groups: ≤20 years group (n=9),21-30 years group (n=54),31-40 years group (n=60),41-50 years group (n=34) and>51 years group (n=14). The spinal cord function was assessed based on the American Spinal Injury Association (ASIA) Classification System before and 2-8 weeks after OECs transplantation. One-way ANOVA and q test were used for statistical analysis,and the data were expressed as mean±SD. Results After surgery,the motor scores increased by 5.2±4.8,8.6±8.0,8.3±8.8,5.7±7.3 and 8.2±7.6 in 5 age groups respectively ( F =1.009,P =0.404); light touch scores increased by 13.9±8.1,15.5±14.3,12.0±14.4,14.1±18.5 and 24.8±25.3 respectively ( F =1.837,P =0.124); and pin prick scores increased by 11.1±7.9,17.2±14.3,13.2±11.8,13.6±13.9 and 25.4±24.3 respectively ( F =2.651,P =0.035). Restoration of pin prick in >51 years group was better than other age groups except 21-30 years group. Conclusion OECs transplantation can improve the neurological function of spinal cord of SCI patients regardless of their ages. Further research into the long-term outcomes of the treatment will be required.

Functional recovery after rhesus monkey spinal cord injury by transplantation of bone marrow mesenchymal-stem cell-derived neurons

Background The treatment of spinal cord injury is still a challenge. This study aimed at evaluating the therapeutical effectiveness of neurons derived form mesenchymal stem cells （MSCs） for spinal cord injury. Methods In this study, rhesus MSCs were isolated and induced by cryptotanshinone in vitro and then a process of RT-PCR was used to detect the expression of glutamic acid decarboxylase （GAD） gene. The induced MSCs were tagged with Hoechst 33342 and injected into the injury site of rhesus spinal cord made by the modified Allen method. Following that, behavior analysis was made after 1 week, 1 month, 2 months and 3 months. After 3 months, true blue chloride retrograde tracing study was also used to evaluate the reestablishment of axons pathway and the hematoxylin-eosin （HE） staining and immunohistochemistry were performed after the animals had been killed. Results In this study, the expression of mRNA of GAD gene could be found in the induced MSCs but not in primitive MSCs and immunohistochemistry could also confirm that rhesus MSCs could be induced and differentiated into neurons. Behavior analysis showed that the experimental animals restored the function of spinal cord up to grade 2 -3 of Tarlov classification. Retrograde tracing study showed that true blue chollide could be found in the rostral thoracic spinal cords, red nucleus and sensory-motor cortex. Conclusions These results suggest that the transplantation is safe and effective.