title: Co-delivery of G-CSF and EPO released from fibrin gel for therapeutic neovascularization in rat hindlimb ischemia model.
abstract: OBJECTIVE
  G-CSF and EPO have shown a notable capability in neovascularization. However, their use is limited because of untoward leucocytosis, erythrogenesis, and short half-life in the plasma. Herein, we examined whether G-CSF and EPO released from fibrin gel injected into ischemic tissues would synergistically promote neovascularization with limited systematic effects in a rat hindlimb ischemic model.
  
  
  RESULTS
  In vivo study, group Gel received an intramuscular injection of fibrin gel; group Gel+G-CSF received fibrin gel containing human G-CSF; group Gel+EPO received fibrin gel containing human EPO; group Gel+G-CSF&EPO received fibrin gel containing G-CSF and EPO; group G-CSF&EPO received G-CSF and EPO. Through promoting the expression of SDF-1, local high concentration of EPO could traffic CXCR4+ cells mobilized by G-CSF to enhance neovascularization in ischemic muscle. The treatment with Gel+G-CSF&EPO was superior to the other treatments on blood flow reperfusion, capillary density, and α smooth muscle actin-positive vessel density. And this treatment induced a modest WBC count increase in peripheral blood.
  
  
  CONCLUSIONS
  G-CSF and EPO released from fibrin gel had a combined effect on postischemia neovascularization. This treatment may be a novel therapeutic modality for ischemic peripheral artery disease.
authors.affiliation: Department of Vascular Surgery, the second affiliated Hospital, Nanchang University, Nanchang, China. cf970422@126.com
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.forename: Qi
authors.initials: Q
authors.lastname: Liu
authors.forename: Zhen D
authors.initials: ZD
authors.lastname: Zhang
authors.forename: Xian H
authors.initials: XH
authors.lastname: Zhu
mesh_terms: D000818:Animals; D054377:Chemokine CXCL12 / Q000096:biosynthesis; D004359:Drug Therapy, Combination; D004921:Erythropoietin / Q000494:pharmacology*; D005337:Fibrin / Q000494:pharmacology*; D005782:Gels / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006614:Hindlimb / Q000098:blood supply* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007511:Ischemia / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D058729:Peripheral Arterial Disease / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C575935:CXCL12 protein, rat; D054377:Chemokine CXCL12; C554270:EPO protein, human; D005782:Gels; D004921:Erythropoietin; D016179:Granulocyte Colony-Stimulating Factor; D005337:Fibrin
keywords: erythropoietin; fibrin; granulocyte colony stimulating factor; ischemia; neovascularization