title: Benefit of combined extracorporeal shock wave and bone marrow-derived endothelial progenitor cells in protection against critical limb ischemia in rats.
abstract: OBJECTIVE
  We hypothesized that combined treatment with extracorporeal shock wave and bone marrow-derived endothelial progenitor cells might exert enhanced protection against critical limb ischemia in rats.
  
  
  METHODS
  Male Sprague-Dawley rats (n = 9 for laser Doppler study and n = 6 for laboratory examinations in each group) were divided into group 1 (sham control), group 2 (critical limb ischemia treated with culture medium), group 3 (critical limb ischemia treated with intramuscular bone marrow-derived endothelial progenitor cells [2.0 × 10 cells]), group 4 (critical limb ischemia treated with extracorporeal shock wave [280 impulses at 0.1 mJ/mm]), and group 5 (combined bone marrow-derived endothelial progenitor cell-extracorporeal shock wave) after critical limb ischemia induction.
  
  
  RESULTS
  By day 21, laser Doppler showed substantially lower ratios of ischemic/normal blood flow in group 2 compared with other groups (p < .001). The protein expressions of mitochondrial cytochrome c, stromal cell-derived factor-1, C-X-C chemokine receptor type 4, vascular endothelial growth factor, and endothelial nitric oxide synthase were remarkably higher in group 5 than in groups 2 to 4, and notably higher in groups 3 and 4 than in group 2 (all p < .01). The messenger RNA expressions of proinflammatory and apoptotic biomarkers and oxidative stress were reduced in group 5 compared with groups 2 to 4, and notably lower in groups 3 and 4 than in group 2 (all p < .01). The messenger RNA expressions of anti-inflammatory and antiapoptotic biomarkers were lower in group 2 than in other groups (all p < .01). Immunofluorescent staining showed higher numbers of CD31+ stromal cell-derived factor-1+, chemokine receptor type 4+, and von Willebrand factor+ cells, and vessels in the ischemic area in group 5 than in groups 2 to 4, and in groups 3 and 4 than in group 2 (all p < .04).
  
  
  CONCLUSIONS
  Combined treatment with bone marrow-derived endothelial progenitor cells and extracorporeal shock wave is superior to either bone marrow-derived endothelial progenitor cells or extracorporeal shock wave alone in improving ischemia in rodent critical limb ischemia.
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Kuo-Ho
authors.initials: KH
authors.lastname: Yeh
authors.forename: Jiunn-Jye
authors.initials: JJ
authors.lastname: Sheu
authors.forename: Yu-Chun
authors.initials: YC
authors.lastname: Lin
authors.forename: Cheuk-Kwan
authors.initials: CK
authors.lastname: Sun
authors.forename: Li-Teh
authors.initials: LT
authors.lastname: Chang
authors.forename: Ying-Hsien
authors.initials: YH
authors.lastname: Kao
authors.forename: Chia-Hong
authors.initials: CH
authors.lastname: Yen
authors.forename: Pei-Lin
authors.initials: PL
authors.lastname: Shao
authors.forename: Tzu-Hsien
authors.initials: TH
authors.lastname: Tsai
authors.forename: Yung-Lung
authors.initials: YL
authors.lastname: Chen
authors.forename: Sarah
authors.initials: S
authors.lastname: Chua
authors.forename: Steve
authors.initials: S
authors.lastname: Leu
authors.forename: Hon-Kan
authors.initials: HK
authors.lastname: Yip
mesh_terms: D000818:Animals; D015153:Blotting, Western; D018031:Connexin 43 / Q000378:metabolism; D042783:Endothelial Cells / Q000637:transplantation; D005121:Extremities / Q000098:blood supply; D005434:Flow Cytometry; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006412:Hematopoietic Stem Cells / Q000502:physiology; D019220:High-Energy Shock Waves / Q000627:therapeutic use*; D016753:Interleukin-10 / Q000378:metabolism; D007511:Ischemia / Q000517:prevention & control*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D012039:Regional Blood Flow; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D018031:Connexin 43; D017395:Plasminogen Activator Inhibitor 1; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D052250:Nitric Oxide Synthase Type III; D020780:Matrix Metalloproteinase 9