Abstract:Ischemic stroke is a common and frequently occurring disease, with high morbidity and mortality, which seriously threatens human health. At present, the common clinical treatment is mainly focused on various measures to improve cerebral circulation, such as thrombolysis, antithrombotic therapy, antiplatelet therapy, defibrinogen therapy, haemodilution and so on. The irreversible injury of neurons is the main reason for the difficulty of achieving satisfactory results. In recent years, the technology of isolation and cultivation of neural stem cells with potential for self-renewal and differentiation has gradually matured in vitro. More and more researches show that the transplantation of neural stem cells into ischemic stroke animal models can achieve effective treatment. In this paper, the biological characteristics of neural stem cells and the mechanism and progress of neural stem cell transplantation for ischemic stroke are reviewed.

Abstract:Aim To investigate the involvement of stromal cell-derived factor-1(SDF-1)/CXCR4 Axis in recruitment of endothelial progenitor cell(EPC)and reendotheliazation after vascular injury.Methods EPC migration induced by SDF-1α was determined with modified Boyden chamber assay.Treatment of mice after carotid injury with EPC or EPC coincubated with AMD3100(an antagonist of CXCR4),recruitment of EPC,reendotheliazation and neointimal lesion area were determined 14 d later.Results SDF-1α profoundly enhanced EPC migration(p<0.01),but could not enhance migration of EPC treated with AMD3100(p>0.05).Transfused EPC were strictly restricted to the injury site(14.2±3.6 cell/section),and lectin binding confirmed the endothelial phenotype,but only few EPC coincubated with AMD3100 were recruited to the injury site(4.0±2.5 cells/section).Treatment with EPC caused enhanced reendothelialization(83.45%±5.44%,p<0.01)associated with a reduction of neointima formation(19 237±1 875 μm2,p<0.01)compared with isotype control(66.46%±6.16%,34 676±2 412 μm2);treatment with EPC coincubated with AMD3100 caused no enhanced reendothelialization(68.02%±6.68%,p>0.05)and no reduction of neointima formation(32 451±2 081 μm2,p>0.05)compared with isotype control.Conclusions Stromal cell-derived factor-1/CXCR4 Axis plays an instrumental role in recruitment of EPC and reendotheliazation after vascular injury in mice.

Abstract:Aim To investigate the impact by delivery of different number of endothelial progenitor cells(EPC)on repair of injured vessels.Methods Mononuclear cells(MNC)were isolated from rabbit peripheral blood by density-gradient centrifugation.MNC were cultured in endothelial growth medium for 7 days,yielding EPC.Autologous EPC(5×105 cells or 2×105 cells in 100 μL saline)or 100 μL saline alone(control)were administered into a rabbit model of balloon carotid injury.Meanwhile the cells were labeled by CM-DiI for cells tracking.Four weeks after transplantation,rabbits were killed.Fluorescence-labeled EPC,endothelial regeneration rate and interal area/media area(IA/MA)ratio were detected.Results Four weeks after transplantation,fluorescence-labeled EPC were detected within the media,neointima and on the luminal surface of injured vessel.Local transplantation of EPC compared with saline administration markedly accelerated endothelialization of denuded vessel,especially in the group of 5×105 EPC.Meanwhile EPC treatment significantly reduced neointimal formation.Conclusions Delivery of EPC to balloon-injured arteries is associated with accelerated reendothelialization and reduced neointimal formation.More notable effect may turn out when larger number of EPC are deliverd.

Abstract:Aim To investigate the survival and differentiation of mesechymal stem cells(MSC) in infarcted myocardium induced by 5-aza-2-deoxycytidine(5-aza-CdR) and their effects on infarction-induced heart failure of rats.The chronic development was also studied. Methods MSC of Wistar rat were cultured in vitro and the second passage MSC were incubated together with 5-aza-CdR(0.3 μmol/L) for twice.Then the induced MSC labeled with bromodeoxyuridine(BrdU) were transplanted into the infarcted myocardium of rats in the model of infarction-induced heart failure.The rats receiving serum-free medium injection were used as controls.Before transplantation and 1,2,3 month(s) after transplantation,the parameters of heart function,such as ejection fraction(EF),were examined by echocardiography and the survival and differetiation of transplanted MSC were observed by double-lable immunohistochemistry and electric microscope.Chronic changes were observed for 3 months. Results One month after transplantation,the EF value of MSC transplanted group(83.3%±8.1%,n=13)was higher than that of control group(47.2%±11.8%,n=12)(p<0.01).The heart function of MSC transplanted group was also improved compared with that before transplantation(EF=64.3%±10.4%,p<0.01).The heart function of MSC transplanted group sustained during 3 months observation.The EF value was 83.1%±14.4%(n=7) and 86.3%±3.7%(n=6) respectively 2 and 3 months after transplantation.While in serum-free medium transplanted group,the EF value was 51.6%±11.2%(n=6) and 49.1%±7.7%(n=6) respectively 2 and 3 months after transplantation.There was significant difference between two groups 2 and 3 months after transplantation(p<0.01).The Transplanted cells were survival in myocardial scar.Double-lable immunohistochemistry showed that BrdU and TroponinT of them were positive.Electric microscope showed that they had some peculiarity of cardiomyocytes 1 month after transplantation.But the nuclear was big and the cytoplasm was little.No sarcomeres and Z-bands could be found.3 months after transplantation,Z-bands could be found in the transplanted cells. Conclusion 5-aza-CdR induced MSC could improve the function in infarction-induced heart failure of rats,and the effect could sustain during 3 months observation.They could survive in the infarct scar of rats and differentiate into cardiomyocytes gradually.

Abstract:During the last few years stem cells including skeletal myoblasts, embryonic stem cells and bone marrow-derived stem cells have been proposed for myocardial regeneration. The experimental studies in animal models of infarction have documented the efficacy of stem cell transplantation in improving function of infarcted myocardium although the mechanisms involved in this improvement are not elucidated. This comment will try to present an overview of encouraging data, focus and questions on stem cells for treatment of myocardial infarction. I also provide my insight into the clinical potential for stem cell implantation.