Effect of transplantation of hMSCs modified by BDNF and GDNF gene on injured brain in rat MCAO model

AIM：To study the therapeutic effect of human mesenchymal stem cells (hMSCs) modified by brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) gene transfer with liposome on middle cerebral artery occlusion (MCAO) model rats. METHODS：The nonviral expression vector was constructed and transfected into the hMSCs by liposomal method. The rat brain injury model was established by the method of MCAO. The gene-modified hMSCs, control hMSCs or PBS was transplanted into the rats 24 h after MCAO by femoral venous injection. The neurological function score, the change of the body weight and the behavior test were used to evaluate the damage of the brain in the rats. The degree of the damage and the migration of the cells 15 d after transplantation were analyzed by observing the histological changes of the brain tissues. RESULTS：The expression levels of BDNF and GDNF in gene-modified hMSCs were much higher than those in control hMSCs. The transplantation of BDNF and GDNF gene-modified hMSCs promoted the functional recovery and reduced the infarct size in the rats after MCAO. A few exogenesis cells only survived in the infarct area of the brain in the MCAO rats, and the cells showed no differentiation. CONCLUSION：Transplantation of BDNF and GDNF gene-modified hMSCs by nonviral expression vector is effective in treating cerebral ischemia. The effect may result from the action of the cytokines secreted by these cells, reducing the injuries induced by the brain ischemia and accelerating the nerve repair following the injury.