title: Cotreatment with darbepoetin and granulocyte colony-stimulating factor is efficient to recruit proangiogenic cell populations in patients with acute myocardial infarction.
abstract: To determine whether newer combination cytokine treatment with granulocyte colony-stimulating factor (G-CSF) and darbepoetin can improve efficacy of stem cell therapy, we evaluated safety and peripheral blood stem/progenitor cell (PBSC) mobilizing effects of combination cytokine in  comparison with G-CSF alone in patients with acute myocardial infarction (AMI). We randomized 60 patients with AMI into two groups under 2:1 ratio; combination treatment with darbepoetin and G-CSF (n = 41: Combicytokine group) and the G-CSF alone (n = 19: G-CSF group). After  coronary angioplasty, G-CSF was treated for 3 days with dose of 10 μg/kg/day in both groups. Only in the combicytokine group, additional single intravenous injection of 4.5 μg/kg of darbepoetin was administrated immediate after coronary angioplasty. Combination cytokine treatment was  well tolerated as was G-CSF alone. PBSCs were obtained by apheresis for intracoronary infusion after completion of cytokine treatment and were analyzed by flow cytometry. The purity of proangiogenic cells was higher in combination cytokine group than the G-CSF group. Specifically, proportion  of CD34(+)/KDR(+) endothelial progenitor cells, CD3(+)/CD31(+) angiogenic T cells and Tie2(+)/CXCR4(+) cells in apheresis products were higher in the combicytokine group. These meant that the combicytokine treatment recruited PBSCs in higher  purity and fewer unwanted inflammatory cells than G-CSF alone in apheresis products. Combination treatment with darbepoetin and G-CSF is safe and more efficient to mobilize and recruit proangiogenic cells than G-CSF alone in patients with AMI. (
  
  
  BACKGROUND
  www.ClinicalTrials. gov identifier:  NCT00501917).
authors.affiliation: Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
authors.forename: Hyun-Jae
authors.initials: HJ
authors.lastname: Kang
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Yoon
authors.forename: Eun-Ju
authors.initials: EJ
authors.lastname: Lee
authors.forename: Min-Kyung
authors.initials: MK
authors.lastname: Kim
authors.forename: Jung-Won
authors.initials: JW
authors.lastname: Suh
authors.forename: Kyung-Woo
authors.initials: KW
authors.lastname: Park
authors.forename: Hae-Young
authors.initials: HY
authors.lastname: Lee
authors.forename: Kyoung Un
authors.initials: KU
authors.lastname: Park
authors.forename: Young-Seok
authors.initials: YS
authors.lastname: Cho
authors.forename: Bon-Kwon
authors.initials: BK
authors.lastname: Koo
authors.forename: In-Ho
authors.initials: IH
authors.lastname: Chae
authors.forename: Dong-Ju
authors.initials: DJ
authors.lastname: Choi
authors.forename: Kyu-Sup
authors.initials: KS
authors.lastname: Han
authors.forename: Hyo-Soo
authors.initials: HS
authors.lastname: Kim
authors.forename: Young-Bae
authors.initials: YB
authors.lastname: Park
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000378:metabolism; D001781:Blood Component Removal; D017023:Coronary Angiography; D000068256:Darbepoetin alfa; D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular / Q000166:cytology; D004921:Erythropoietin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006397:Hematinics / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy*; D042787:Receptor, TIE-2 / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism
chemical_list: D018952:Antigens, CD34; D006397:Hematinics; D004921:Erythropoietin; D016179:Granulocyte Colony-Stimulating Factor; D000068256:Darbepoetin alfa; D042787:Receptor, TIE-2