title: Mononuclear cell therapy reverts cuff-induced thrombosis in apolipoprotein E-deficient mice.
abstract: BACKGROUND
  Stem/progenitor cell-based therapy has successfully been used as a novel therapeutic strategy for vascular diseases triggered by endothelial dysfunction. The aim of this study was to investigate the effects of mononuclear cell (MNC) therapy in situ on carotid cuff-induced occlusive thrombus in the apolipoprotein E knockout (apoE-/-) mouse.
  
  
  METHODS
  Spleen-derived MNCs were isolated from green fluorescent protein (GFP)-transgenic mice for cell treatment. A cuff-induced thrombus model was produced by placing a nonconstrictive silastic collar around the left common carotid artery in 20-week-old female apoE-/- mice. After 10 days, the cuff was removed, and the animals received in situ MNCs (Cuff-MNC) or vehicle (Cuff-Vehicle) and were compared with sham-operated animals (Sham).
  
  
  RESULTS
  The histological analysis showed that the MNC treatment reverted occlusive thrombus formation compared to the vehicle and the vessel lumen area to that observed in the Sham group (MNC, 50 ± 4; Vehicle, 20 ± 4; Sham, 55 ± 2 x10³ μm²; p < 0.01). The animals that underwent the carotid cuff placement developed compensatory vessel enlargement, which was reduced by the MNC therapy. In addition, the treatment was able to reduce superoxide anion production, which likely contributed to the reduced apoptosis that was observed. Lastly, the immunofluorescence analysis revealed the presence of endothelial progenitor cells (EPCs) in the carotid endothelia of the apoE-/- mice.
  
  
  CONCLUSIONS
  In situ short-term MNC therapy was able to revert cuff-induced occlusive thrombi in the carotid arteries of apoE-/- mice, possibly through the homing of EPCs, reduction of oxidative stress and decreased apoptosis.
authors: Laboratory of Transgenes and Cardiovascular Control, Department Physiological Sciences, Health Sciences Center, Federal University of Espirito Santo, Vitoria, ES, Brazil.
authors: Leandro C F
authors: LC
authors: Lima
authors: Marcella L
authors: ML
authors: Porto
authors: Bianca P
authors: BP
authors: Campagnaro
authors: Clarissa L
authors: CL
authors: Tonini
authors: Breno V
authors: BV
authors: Nogueira
authors: Thiago Mc
authors: TM
authors: Pereira
authors: Elisardo C
authors: EC
authors: Vasquez
authors: Silvana S
authors: SS
authors: Meyrelles
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D017209:Apoptosis; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology; D017536:Carotid Artery, Common / Q000473:pathology; D042783:Endothelial Cells / Q000473:pathology; D005260:Female; D049452:Green Fluorescent Proteins / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000637:transplantation*; D008026:Ligation; D051379:Mice; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D018384:Oxidative Stress; D011994:Recombinant Proteins / Q000096:biosynthesis; D013481:Superoxides / Q000378:metabolism; D013927:Thrombosis / Q000209:etiology / Q000628:therapy*
chemical_list: D001057:Apolipoproteins E; D011994:Recombinant Proteins; D013481:Superoxides; D049452:Green Fluorescent Proteins