title: Effects of transplantation with bone marrow-derived mesenchymal stem cells modified by Survivin on experimental stroke in rats.
abstract: BACKGROUND
  This study was performed to determine whether injury induced by cerebral ischemia could be further improved by transplantation with bone marrow-derived mesenchymal stem cells (MSCs) modified by Survivin (SVV).
  
  
  METHODS
  MSCs derived from bone marrow of male Sprague-Dawley rats were infected by the self-inactive lentiviral vector GCFU carrying green fluorescent protein (GFP) gene and SVV recombinant vector (GCFU-SVV). In vitro, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) were detected in infected MSCs supernatants under hypoxic conditions by ELSIA. In vivo, experiments consisted of three groups, one receiving intravenous injection of 500 μl of phosphate-buffered saline (PBS) without cells (control group) and two groups administered the same volume solution with either three million GFP-MSCs (group GFP) or SVV/GFP-MSCs (group SVV). All animals were submitted to 2-hour middle cerebral artery occlusion (MCAO) and then reperfusion. Differentiation and survival of the transplanted MSCs were determined by confocal microscope. Western blot was used to detect the expression of VEGF and bFGF in ischemic tissue. A 2,3,5-triphenyltetrazolium chloride (TTC) staining was used to assess the infarct volume. Evaluation of neurological function was performed using a modified Neurological Severity Score (mNSS).
  
  
  RESULTS
  In vitro, modification with SVV further increased secretion of VEGF and bFGF under hypoxic condition. In vivo, only very few transplantated cells co-expressed GFP and NeuN. The survival transplanted cells in the group SVV was 1.3-fold at 4 days after transplantation and 3.4-fold higher at 14 days after transplantation, respectively, when compared with group GFP. Expression of VEGF and bFGF in the ischemic tissue were further up-regulated by modification with SVV. Moreover, modification with SVV further reduced the cerebral infarct volume by 5.2% at 4 days after stroke and improved post-stroke neurological function at 14 days after transplantation.
  
  
  CONCLUSIONS
  Modification with SVV could further enhance the therapeutic effects of MSCs possibly through improving the MSCs survival capacity and up-regulating the expression of protective cytokines in the ischemic tissue.
authors: Department of Neurology, Union Hospital, Fujian Medical University, Fuzhou 350001, PR China. xieheliunan1984@sina.com.cn
authors: Nan
authors: N
authors: Liu
authors: Yixian
authors: Y
authors: Zhang
authors: Lin
authors: L
authors: Fan
authors: Mingzhou
authors: M
authors: Yuan
authors: Houwei
authors: H
authors: Du
authors: Ronghua
authors: R
authors: Cheng
authors: Deshan
authors: D
authors: Liu
authors: Feifei
authors: F
authors: Lin
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D001921:Brain / Q000473:pathology; D020520:Brain Infarction / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D002454:Cell Differentiation; D002470:Cell Survival; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics* / Q000627:therapeutic use*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D010641:Phenotype; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D000077022:Survivin; D014161:Transduction, Genetic; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D000077022:Survivin; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2