Role of NT-3 gene modified mesenchymal stem cells and its mechanism in treatment of acute cerebral infarction

Objective To investigate the role of neurotrophin-3 (NT-3) gene modified bone marrow mesenchymal stem cells (BMSCs) in treatment of acute cerebral infarction and its underlying mechanism. Methods Seventy-two SD male rats were randomly divided into model group, BMSCs group, and BMSCs+NT-3 group (n=24). Focal cerebral ischemia rat models were established by middle cerebral artery occlusion (MCAO); 24 h after MCAO, rats in the BMSCs group and BMSCs+NT-3 group were given BMSCs and NT-3 gene modified BMSCs via tail intravenous injection, respectively. Modified neurological severity scale (mNSS) was performed one, 6, 12 and 24 d after MCAO; infarct sizes were measured by TTC staining one, 12 and 24 d after MCAO; expressions of neuronspecific enolase (NSE) and nestin in the surrounding areas of infarction were detected by Western blotting 6 d after MCAO. Results As compared with those in the BMSCs group, significantly decreased mNSS scores in BMSCs+NT-3 group were noted 6, 12 and 24 d after MCAO (P<0.05). Rats in the BMSCs+NT-3 group had significantly smaller brain infarct sizes than the BMSCs group 12 and 24 d after MCAO(P<0.05). Expressions of NSE and nestin in the BMSCs+NT-3 group were significantly higher than those in the BMSCs group 6 d after MCAO (P<0.05). Conclusion Transplantation of NT-3 gene modified BMSCs can further improve neurological functions and reduce brain infarct sizes as compared with BMSCs transplantation, whose mechanism might be related to promote the differentiation of BMSCs into neurons. Key words: Bone marrow mesenchymal stem cell; Neurotrophin-3; Gene modification; Stem cell transplantation; Cerebral ischemia