Curative effect of transplantation of mesenchymal stem cells transfected with recombinant lentiviral vectors carrying brain-derived neurotrophic factor gene on intracerebral hemorrhage in rats / 中华神经科杂志

ABSTRACT

Objective To observe the curative effect of transplantation of mesenchymal stem cells (MSCs) transfected with recombinant lentiviral vectors carrying brain-derived neurotrophic factor (BDNF) gene on intracerebral hemorrhage in rats.Methods MSCs were isolated from the rat bone marrow,cultured and transfected by recombinant lentiviral vectors carrying BDNF gene.Intracerebral hemorrhagic models were constructed and randomly divided into 4 groupsphosphate buffered saline transplanted (PBS) group,MSCs group,mesenchymal stem cells transfected with empty lentiviral vectors transplanted (MSCs-EGFP) group and mesenchymal stem cells transfected with recombinant lentiviral vectors carrying brain-derived neurotrophic factor gene transplanted (MSCs-EGFP-BDNF) group.PBS and MSCs were transplanted according to the groups 72 hours after the establishment of models.The improvements of the neurological function were recorded of each group 7 d,14 d,and 21 d after the transplantation.Double labeling immunofluorescent staining were used to detect the migration and the differentiation of transplanted MSCs.Results MSCs-EGFP-BDNF group had significant higher levels of BDNF gene and protein expression than MSCs group and MSCs-EGFP group.All MSCs transplanted groups (MSCs groups7 d1.6 ±0.2,14 d1.2 ±0.3,21 d0.8 ±0.2; MSCs-EGFP groups7 d1.6 ±0.3,14 d1.1 ±0.2,21 d0.8 ±0.3; MSCs-EGFP-BDNFgroup7 d1.2 ±0.3,14 d0.6 ±0.1,21 d0.2±0.2) had more improvements in the neural function (F=6.667,18.417,20.882,all P ＜0.05) than PBS group(7 d2.0 ±0.4,14 d1.7 ±0.2,21 d1.3 ±0.2),and MSCs-EGFP-BDNF group had the most significant improvement.With double labeling immunofluorescent staining,the MSCs-EGFP-BDNF group had significantly higher positive rates of glial fibrilary acidicprotein,neuron specific nuclear protein,2',3 '-cyclic nucleotide 3'-phosphodiesterase than MSCs group and MSCs-EGFP group,while there was no significant differences between the latter two.Conclusions The expression levels of gene and protein are higher for the MSCs modified with recombinant lentiviral vectors carrying BDNF gene.The modified MSCs can migrate to the perihematomal brain issue of intracerebral hemorrhage,express the characteristic molecules of neurons and improve the neural function after intracerebral hemorrhage.