title: Overexpression of CXCR4 in mesenchymal stem cells promotes migration, neuroprotection and angiogenesis in a rat model of stroke.
abstract: BACKGROUND
  Stromal cell-derived factor-1 (SDF-1) and its cognate receptor, chemokine (C-X-C motif) receptor 4 (CXCR4), are involved in the migration of stem cells.
  
  
  OBJECTIVE
  To test the hypothesis that mesenchymal stem cells (MSCs) with genetically modified CXCR4 can promote their own recruitment around the ischemic core.
  
  
  METHODS
  Lentiviral vectors were used to overexpress the CXCR4-eGFP fusion protein (CXCR4/eGFP) or eGFP only (eGFP) or to introduce siRNA targeting endogenous CXCR4 (siRNA/eGFP) in rat mesenchymal stem cells (rMSCs). Rats were injected with either the transduced rMSCs or PBS as a control via the femoral vein following a left middle cerebral artery occlusion (MCAO).
  
  
  RESULTS
  One week after MCAO, immunofluorescence staining revealed a significant increase in the number of eGFP-positive cells surrounding the infarct areas in the CXCR4-rMSC-treated group compared to the rMSC-treated control group. Conversely, there was a significant reduction in the number of eGFP-positive cells in the siRNA-rMSC-treated group. Moreover, there was an increase in the capillary vascular volume of the peri-infarct area, a reduction in the volume of the cerebral infarction and improved neurological function in the CXCR4-rMSC-treated group compared to those in the rMSC-, siRNA-rMSC- or PBS-treated groups.
  
  
  CONCLUSIONS
  CXCR4 overexpression in the rMSCs promoted their mobilization and enhanced neuroprotection in a rat cerebral ischemia model. This strategy may be a useful therapeutic approach for treating ischemic stroke.
authors.affiliation: Department of Neurology, First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, China.
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Yu
authors.forename: Dongping
authors.initials: D
authors.lastname: Chen
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xiuli
authors.initials: X
authors.lastname: Wu
authors.forename: Zhixing
authors.initials: Z
authors.lastname: Huang
authors.forename: Haitao
authors.initials: H
authors.lastname: Zhou
authors.forename: Yanding
authors.initials: Y
authors.lastname: Zhang
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000235:genetics*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D018919:Neovascularization, Physiologic / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019718:Receptors, CXCR4 / Q000096:biosynthesis* / Q000235:genetics; D020521:Stroke / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: C486264:Cxcr4 protein, rat; D019718:Receptors, CXCR4